Current Psychiatry

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/therapeutic-neuromodulation.html#comments

The brain is an electrochemical organ, and its activity can be modulated for therapeutic purposes by electrical, pharmacologic, or combined approaches. In general, neuromodulation induces electrical current in peripheral or central nervous tissue, which is accomplished by various techniques, including:

• electroconvulsive therapy (ECT)
• vagus nerve stimulation (VNS)
• transcranial magnetic stimulation (TMS)
• deep brain stimulation (DBS).

It is thought that therapeutic benefit occurs by regulating functional disturbances in relevant distributed neural circuits.¹ Depending on the stimulation method, the frequencies chosen may excite or inhibit different or the same areas of the brain in varying patterns. Unlike medication, neuromodulation impacts the brain episodically, which may mitigate adaptation to the therapy’s beneficial effects and avoid systemic adverse effects.

Neuromodulation techniques are categorized based on their risk level as invasive or noninvasive and seizurogenic or nonseizurogenic (Table 1). Although these and other approaches are being considered for various neuropsychiatric disorders (Table 2), the most common application is for severe, treatment-resistant depression. Therefore, this article focuses on FDA-approved neuromodulation treatments for depression, with limited discussion of other indications.

Table 1

Therapeutic neuromodulation: Categorization based on risk

Table 2

Approved and investigational indications of neuromodulation

ECT: Oldest and most effective

ECT has remained the most effective therapeutic neuromodulation technique for more than 7 decades. It is indicated primarily for severe depressive episodes (eg, psychotic, melancholic), particularly in older patients.

ECT delivers electrical current to the CNS that is sufficient to produce a seizure. Under modified conditions, a typical course of 6 to 12 sessions can resolve severe depressive episodes and may also benefit other disorders, such as bipolar mania and acute psychosis. Although ECT is potentially life-saving, its use was markedly curtailed with the advent of effective antidepressants in the 1950s. Multiple factors impede its use, including:

• access and expertise are limited in many areas
• cognition is at least temporarily adversely affected
• relapse rates after acute benefit are high
• cost
• public perception often is negative.

Studies are addressing several of these concerns. For example, the National Institute of Mental Health-sponsored Consortium on Research with ECT (CORE) group is considering how to more effectively maintain acute benefits of ECT. They compared the potential merits of maintenance ECT with maintenance pharmacotherapy (nortriptyline plus lithium) over 6 months. Although the 2 strategies had comparable results, retention rates were <50% and about one-third relapsed in both groups.^2,3 Potential alternative strategies include a more frequent ECT maintenance schedule and/or combining maintenance ECT with medication(s).

Magnetic seizure therapy (MST) and focal electrically administered seizure therapy (FEAST) are attempts to produce similar efficacy and less cognitive disruption compared with ECT.^4,5 Work also continues on electrode placement (eg, bifrontal) and alteration of waveform characteristics (eg, ultra-brief) to maintain or enhance efficacy while minimizing adverse effects.^6,7

Stimulating the vagus nerve

VNS was introduced for treating refractory epilepsy in 1997. In 2005, it became the first FDA-approved implantable device for managing chronic or recurrent treatment-resistant depression.

The vagus nerve is the principal parasympathetic, efferent tract regulating heart rate, intestinal motility, and gastric acid secretion. Information about pain, hunger, and satiety is conveyed by these fibers to the median raphe nucleus and locus coeruleus, brain regions with significant serotonergic and noradrenergic innervation. These neurotransmitters also are believed to play a pivotal role in major depression.

With VNS, a pacemaker-like pulse generator is surgically implanted subcutaneously in the patient’s upper left chest. Wires extend from this device to the left vagus nerve (80% of whose fibers are afferent) located in the neck, to which the pulse generator sends electrical signals every few seconds (Table 3). The right vagus nerve is not used because it provides parasympathetic innervation to the heart. A clinician adjusts stimulation parameters using a computer and a noninvasive handheld device. Common adverse effects include voice alteration or hoarseness, cough, and shortness of breath, which occur during active stimulation because of the proximity of the electrodes to the laryngeal and pharyngeal branches of the vagus nerve. These effects may improve by adjusting stimulation intensity. The device permits a wide range of duty cycles, but preclinical animal studies indicate that >50% activation periods may damage the vagus nerve. If patients become too uncomfortable, they may deactivate the device with a magnet held over the implantation area.

Two open-label studies evaluated VNS to treat major depression. The first involved 10 weeks of stimulation in 59 subjects with chronic or recurrent, nonpsychotic, unipolar or bipolar depression who failed at least 2 adequate antidepressant trials in the current episode.⁸ Stable doses of concomitant antidepressants or mood stabilizers were allowed. After 3 months, 18 (31%) patients responded within an average of 45.5 days, and nearly 15% achieved remission. Response was defined as 50% reduction in baseline Hamilton Depression Rating Scale-28 (HDRS-28) score; remission was defined as HDRS-28 score ≤10. Further, clinical response did not differ between unipolar and bipolar depression patients.

In the second trial, 74 patients with treatment-resistant depression received fixed dose antidepressants and VNS for 3 months, followed by 9 months of flexibly dosed VNS and antidepressants.⁹ At 3 months, response (≥50% reduction in HDRS-28 score) and remission (HDRS-28 score <10) rates were 37% and 17%, respectively, and increased to 53% and 33% at 1 year.

A sham-controlled trial of VNS in 235 depressed patients used similar inclusion and exclusion criteria as in the open-label study by Sackeim et al.^8,10 Two weeks after device implantation, patients were randomized to active treatment (stimulator turned on) or sham control (stimulator left off). At 3 months, the primary outcome measure—response rate based on HDRS-24 score—did not differ significantly between the active and control groups (15% vs 10%, respectively). There was, however, a significantly greater improvement in Inventory of Depressive Symptomatology-Self Report Scale scores with active VNS vs sham VNS.

Patients on sham treatment then were switched to active treatment and both groups were followed for 12 additional months, at which time response and remission rates nearly doubled for both groups.¹¹ In a post-hoc analysis, the same investigators found significant improvement with VNS compared with a naturalistic, matched control group with similar treatment-resistant depression.¹² The FDA considered this adequate to support efficacy and approved the device for chronic or recurrent treatment-resistant depression in an episode not responsive to at least 4 adequate treatment trials with pharmacotherapy or ECT. Perhaps because post-hoc analyses typically are not sufficient to gain FDA approval, most insurance companies do not reimburse for VNS treatment of depression, and VNS is not frequently used for refractory depression.

Table 3

Vagus nerve stimulation treatment parameters

A newer option: TMS

TMS is the most recently FDA-approved therapeutic neuromodulation technique for treating depression. In October 2008, a TMS device became available for patients failing to respond to 1 adequate antidepressant trial during the current episode.

TMS delivers intense, intermittent magnetic pulses produced by an electrical charge into a ferromagnetic coil. The pulse intensity is similar to that produced by MRI. The coil usually is placed on the scalp over the left dorsolateral prefrontal cortex (DLPFC) and pulses are delivered in a rapid, repetitive train, causing neuronal depolarization in a small area of the adjacent cerebral cortex, as well as distal effects in other relevant neural circuits (Table 4). TMS typically is administered on an outpatient basis. A standard treatment course for depression consists of 5 treatment sessions per week for 4 to 8 weeks, depending on symptom severity and how quickly patients respond.

TMS initially was examined in several small, open-label studies that looked at various treatment parameters and stimulation sites. Several sham-controlled studies generally found TMS efficacious and further refined treatment administration. Its role in treating depression—and possibly other psychiatric disorders—has been supported by 2 recent meta-analyses.^13,14

O’Reardon et al¹⁵ conducted the largest double-blind trial of active vs sham TMS (N=301) for moderately treatment-resistant major depression. This study began with a 4- to 6-week, blinded, randomized phase followed by 6 weeks of open-label TMS for initial nonresponders. The third phase reintroduced TMS over 6 months as needed to augment maintenance antidepressants. This trial utilized the most aggressive treatment parameters to date (ie, 10 Hz; 75 4-second trains; 26-second inter-train interval; 120% motor threshold) delivering 3,000 pulses per treatment over an average of 24 sessions. Compared with the sham procedure, patients who received active TMS showed significantly higher response rates on the Montgomery-Åsberg Depression Rating Scale (MADRS) at weeks 4 and 6. Similar results were found for the 17- and 24-item HDRS. At 6 weeks, remission rate—defined as a MADRS score <10—was significantly higher in the active treatment group (14%) compared with the sham procedure (6%). A post-hoc analysis found that the most robust benefit occurred in patients with only 1 failed adequate antidepressant trial (effect size=0.83).¹⁶ This administration protocol was well tolerated, with no deaths or seizures and a low rate of discontinuation because of adverse events (5%).¹⁷ The most common adverse effects were application site pain or discomfort and headaches.

Recently, the second largest (N=190) sham-controlled trial of TMS for treatment-resistant major depression was published.¹⁸ This National Institute of Mental Health-sponsored, multiphase study included an initial 2-week, treatment-free period; 3 weeks of daily treatments over the left DLPFC using the same device and parameters as in the O’Reardon study; and an additional 3 weeks of treatment in patients who were improving. Those not responding to initial treatment were crossed over to open-label active TMS. This study advanced TMS development by:

• using a novel somatosensory system that produced similar sensations with sham and active TMS
• assessing the success of maintaining the blind
• establishing a rigorous clinical rating system
• utilizing MRI-guided adjustment of coil placement in a subset of patients.

The authors concluded that active TMS was significantly better than sham treatment in achieving remission (14% vs 5%). In addition, the raters, treaters, and patients were effectively blinded to the treatment condition. MRI-assisted coil placement found that in 33% of the sample, site placement determined by standardized assessment was over the premotor cortex rather than the prefrontal cortex, so the coil was moved 1 additional cm anteriorly in these patients. Similar to those observed by O’Reardon et al, adverse effects of active TMS were generally mild to moderate, did not differ by treatment condition, and led to a low discontinuation rate (5.5%).

Table 4

Treatment parameters of transcranial magnetic stimulation

Deep brain stimulation

DBS is a “functional neurosurgical” procedure that delivers electrical current directly to specific areas within the brain.¹⁹ Its mechanism of action remains uncertain; depolarization blockade, synaptic inhibition, and “neural jamming” are leading hypotheses. In contrast to conventional ablative surgeries, DBS is reversible and adjustable. Implantation involves positioning pacemaker-like battery devices subcutaneously in the left and right upper chest. Electrodes attached to wires are run subcutaneously behind the ears and, with stereotactic guidance, placed through burr holes in the skull into specific CNS areas implicated in the pathophysiology of conditions such as Parkinson’s disease, refractory depression, and severe obsessive-compulsive disorder (OCD).

Antidepressant effects. The FDA recently approved DBS under its humanitarian device exemption program for intractable, severe, disabling OCD based on promising results from open and blind trials that stimulated areas such as the internal capsule and adjacent ventral striatum.^20-22 These studies reported that DBS of the caudate nucleus for OCD and subthalamic nucleus for Parkinson’s disease also produced antidepressant effects. Subsequently, trials targeting the subgenual region (Brodmann’s area 25), the ventral capsule/ventral striatum, and nucleus accumbens demonstrated antidepressant effects.^23-27 Pending the results of ongoing pilot trials, large, multi-center studies using different devices and target areas are being planned to clarify the role of DBS for patients with severe, disabling, refractory depression.

Adverse effects of DBS can be:

• surgical-related (eg, seizure, bleeding, infection)
• device-related (eg, lead breakage, malfunction)
• stimulation-related (eg, paresthesia, dysarthria, memory disruption, cognitive changes, psychiatric symptoms).

The most serious risk is intracranial bleeding, which occurs in 2% to 3% of patients. Clearly, the risk-benefit ratio must be carefully considered.

Cost and reimbursement

Cost of treatment and potential for third-party reimbursement are important considerations for any risk-benefit analysis. Many patients who seek neuromodulation treatments will not have insurance or other coverage entitlements.^28-30 Further, newer treatments are not routinely covered by insurance; however, individual case coverage may be allowed and some device manufacturers have programs to assist providers and patients obtain coverage.^28-30 Even ECT, which has long been a covered treatment for major depression, is still considered investigational for other disorders. Thus, it is important to pre-certify with the patient’s health insurance provider before initiating treatment.

Coverage, however, is not the only consideration when weighing cost effectiveness. Economic studies can assist with clinical and ethical decisions relating to treatment choice.³¹ These studies, however, need to be critically evaluated (eg, what costs were included in the analysis). Although direct costs are easier to evaluate, indirect costs—such as the patient’s ability to continue to work while receiving the treatment, caretaker availability during treatment, and whether treatment is an inpatient or outpatient procedure—are more difficult to evaluate and should be discussed with the patient. Because these specialized options have the potential to further benefit patients with depression and other neuropsychiatric disorders, it is essential to balance the pressures of cost containment with the need for more effective and better tolerated treatments.^32-34

Related Resource

• Brunoni AR, Teng CT, Correa C, et al. Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting. Arq Neuropsiquiatr. 2010;68(3):433-451.

Drug Brand Names

• Lithium • Eskalith, Lithobid
• Nortriptyline • Aventyl, Pamelor

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/therapeutic-neuromodulation.html#comments

The brain is an electrochemical organ, and its activity can be modulated for therapeutic purposes by electrical, pharmacologic, or combined approaches. In general, neuromodulation induces electrical current in peripheral or central nervous tissue, which is accomplished by various techniques, including:

• electroconvulsive therapy (ECT)
• vagus nerve stimulation (VNS)
• transcranial magnetic stimulation (TMS)
• deep brain stimulation (DBS).

It is thought that therapeutic benefit occurs by regulating functional disturbances in relevant distributed neural circuits.¹ Depending on the stimulation method, the frequencies chosen may excite or inhibit different or the same areas of the brain in varying patterns. Unlike medication, neuromodulation impacts the brain episodically, which may mitigate adaptation to the therapy’s beneficial effects and avoid systemic adverse effects.

Neuromodulation techniques are categorized based on their risk level as invasive or noninvasive and seizurogenic or nonseizurogenic (Table 1). Although these and other approaches are being considered for various neuropsychiatric disorders (Table 2), the most common application is for severe, treatment-resistant depression. Therefore, this article focuses on FDA-approved neuromodulation treatments for depression, with limited discussion of other indications.

Table 1

Therapeutic neuromodulation: Categorization based on risk

Table 2

Approved and investigational indications of neuromodulation

ECT: Oldest and most effective

ECT has remained the most effective therapeutic neuromodulation technique for more than 7 decades. It is indicated primarily for severe depressive episodes (eg, psychotic, melancholic), particularly in older patients.

ECT delivers electrical current to the CNS that is sufficient to produce a seizure. Under modified conditions, a typical course of 6 to 12 sessions can resolve severe depressive episodes and may also benefit other disorders, such as bipolar mania and acute psychosis. Although ECT is potentially life-saving, its use was markedly curtailed with the advent of effective antidepressants in the 1950s. Multiple factors impede its use, including:

• access and expertise are limited in many areas
• cognition is at least temporarily adversely affected
• relapse rates after acute benefit are high
• cost
• public perception often is negative.

Studies are addressing several of these concerns. For example, the National Institute of Mental Health-sponsored Consortium on Research with ECT (CORE) group is considering how to more effectively maintain acute benefits of ECT. They compared the potential merits of maintenance ECT with maintenance pharmacotherapy (nortriptyline plus lithium) over 6 months. Although the 2 strategies had comparable results, retention rates were <50% and about one-third relapsed in both groups.^2,3 Potential alternative strategies include a more frequent ECT maintenance schedule and/or combining maintenance ECT with medication(s).

Magnetic seizure therapy (MST) and focal electrically administered seizure therapy (FEAST) are attempts to produce similar efficacy and less cognitive disruption compared with ECT.^4,5 Work also continues on electrode placement (eg, bifrontal) and alteration of waveform characteristics (eg, ultra-brief) to maintain or enhance efficacy while minimizing adverse effects.^6,7

Stimulating the vagus nerve

VNS was introduced for treating refractory epilepsy in 1997. In 2005, it became the first FDA-approved implantable device for managing chronic or recurrent treatment-resistant depression.

The vagus nerve is the principal parasympathetic, efferent tract regulating heart rate, intestinal motility, and gastric acid secretion. Information about pain, hunger, and satiety is conveyed by these fibers to the median raphe nucleus and locus coeruleus, brain regions with significant serotonergic and noradrenergic innervation. These neurotransmitters also are believed to play a pivotal role in major depression.

With VNS, a pacemaker-like pulse generator is surgically implanted subcutaneously in the patient’s upper left chest. Wires extend from this device to the left vagus nerve (80% of whose fibers are afferent) located in the neck, to which the pulse generator sends electrical signals every few seconds (Table 3). The right vagus nerve is not used because it provides parasympathetic innervation to the heart. A clinician adjusts stimulation parameters using a computer and a noninvasive handheld device. Common adverse effects include voice alteration or hoarseness, cough, and shortness of breath, which occur during active stimulation because of the proximity of the electrodes to the laryngeal and pharyngeal branches of the vagus nerve. These effects may improve by adjusting stimulation intensity. The device permits a wide range of duty cycles, but preclinical animal studies indicate that >50% activation periods may damage the vagus nerve. If patients become too uncomfortable, they may deactivate the device with a magnet held over the implantation area.

Two open-label studies evaluated VNS to treat major depression. The first involved 10 weeks of stimulation in 59 subjects with chronic or recurrent, nonpsychotic, unipolar or bipolar depression who failed at least 2 adequate antidepressant trials in the current episode.⁸ Stable doses of concomitant antidepressants or mood stabilizers were allowed. After 3 months, 18 (31%) patients responded within an average of 45.5 days, and nearly 15% achieved remission. Response was defined as 50% reduction in baseline Hamilton Depression Rating Scale-28 (HDRS-28) score; remission was defined as HDRS-28 score ≤10. Further, clinical response did not differ between unipolar and bipolar depression patients.

In the second trial, 74 patients with treatment-resistant depression received fixed dose antidepressants and VNS for 3 months, followed by 9 months of flexibly dosed VNS and antidepressants.⁹ At 3 months, response (≥50% reduction in HDRS-28 score) and remission (HDRS-28 score <10) rates were 37% and 17%, respectively, and increased to 53% and 33% at 1 year.

A sham-controlled trial of VNS in 235 depressed patients used similar inclusion and exclusion criteria as in the open-label study by Sackeim et al.^8,10 Two weeks after device implantation, patients were randomized to active treatment (stimulator turned on) or sham control (stimulator left off). At 3 months, the primary outcome measure—response rate based on HDRS-24 score—did not differ significantly between the active and control groups (15% vs 10%, respectively). There was, however, a significantly greater improvement in Inventory of Depressive Symptomatology-Self Report Scale scores with active VNS vs sham VNS.

Patients on sham treatment then were switched to active treatment and both groups were followed for 12 additional months, at which time response and remission rates nearly doubled for both groups.¹¹ In a post-hoc analysis, the same investigators found significant improvement with VNS compared with a naturalistic, matched control group with similar treatment-resistant depression.¹² The FDA considered this adequate to support efficacy and approved the device for chronic or recurrent treatment-resistant depression in an episode not responsive to at least 4 adequate treatment trials with pharmacotherapy or ECT. Perhaps because post-hoc analyses typically are not sufficient to gain FDA approval, most insurance companies do not reimburse for VNS treatment of depression, and VNS is not frequently used for refractory depression.

Table 3

Vagus nerve stimulation treatment parameters

A newer option: TMS

TMS is the most recently FDA-approved therapeutic neuromodulation technique for treating depression. In October 2008, a TMS device became available for patients failing to respond to 1 adequate antidepressant trial during the current episode.

TMS delivers intense, intermittent magnetic pulses produced by an electrical charge into a ferromagnetic coil. The pulse intensity is similar to that produced by MRI. The coil usually is placed on the scalp over the left dorsolateral prefrontal cortex (DLPFC) and pulses are delivered in a rapid, repetitive train, causing neuronal depolarization in a small area of the adjacent cerebral cortex, as well as distal effects in other relevant neural circuits (Table 4). TMS typically is administered on an outpatient basis. A standard treatment course for depression consists of 5 treatment sessions per week for 4 to 8 weeks, depending on symptom severity and how quickly patients respond.

TMS initially was examined in several small, open-label studies that looked at various treatment parameters and stimulation sites. Several sham-controlled studies generally found TMS efficacious and further refined treatment administration. Its role in treating depression—and possibly other psychiatric disorders—has been supported by 2 recent meta-analyses.^13,14

O’Reardon et al¹⁵ conducted the largest double-blind trial of active vs sham TMS (N=301) for moderately treatment-resistant major depression. This study began with a 4- to 6-week, blinded, randomized phase followed by 6 weeks of open-label TMS for initial nonresponders. The third phase reintroduced TMS over 6 months as needed to augment maintenance antidepressants. This trial utilized the most aggressive treatment parameters to date (ie, 10 Hz; 75 4-second trains; 26-second inter-train interval; 120% motor threshold) delivering 3,000 pulses per treatment over an average of 24 sessions. Compared with the sham procedure, patients who received active TMS showed significantly higher response rates on the Montgomery-Åsberg Depression Rating Scale (MADRS) at weeks 4 and 6. Similar results were found for the 17- and 24-item HDRS. At 6 weeks, remission rate—defined as a MADRS score <10—was significantly higher in the active treatment group (14%) compared with the sham procedure (6%). A post-hoc analysis found that the most robust benefit occurred in patients with only 1 failed adequate antidepressant trial (effect size=0.83).¹⁶ This administration protocol was well tolerated, with no deaths or seizures and a low rate of discontinuation because of adverse events (5%).¹⁷ The most common adverse effects were application site pain or discomfort and headaches.

Recently, the second largest (N=190) sham-controlled trial of TMS for treatment-resistant major depression was published.¹⁸ This National Institute of Mental Health-sponsored, multiphase study included an initial 2-week, treatment-free period; 3 weeks of daily treatments over the left DLPFC using the same device and parameters as in the O’Reardon study; and an additional 3 weeks of treatment in patients who were improving. Those not responding to initial treatment were crossed over to open-label active TMS. This study advanced TMS development by:

• using a novel somatosensory system that produced similar sensations with sham and active TMS
• assessing the success of maintaining the blind
• establishing a rigorous clinical rating system
• utilizing MRI-guided adjustment of coil placement in a subset of patients.

The authors concluded that active TMS was significantly better than sham treatment in achieving remission (14% vs 5%). In addition, the raters, treaters, and patients were effectively blinded to the treatment condition. MRI-assisted coil placement found that in 33% of the sample, site placement determined by standardized assessment was over the premotor cortex rather than the prefrontal cortex, so the coil was moved 1 additional cm anteriorly in these patients. Similar to those observed by O’Reardon et al, adverse effects of active TMS were generally mild to moderate, did not differ by treatment condition, and led to a low discontinuation rate (5.5%).

Table 4

Treatment parameters of transcranial magnetic stimulation

Deep brain stimulation

DBS is a “functional neurosurgical” procedure that delivers electrical current directly to specific areas within the brain.¹⁹ Its mechanism of action remains uncertain; depolarization blockade, synaptic inhibition, and “neural jamming” are leading hypotheses. In contrast to conventional ablative surgeries, DBS is reversible and adjustable. Implantation involves positioning pacemaker-like battery devices subcutaneously in the left and right upper chest. Electrodes attached to wires are run subcutaneously behind the ears and, with stereotactic guidance, placed through burr holes in the skull into specific CNS areas implicated in the pathophysiology of conditions such as Parkinson’s disease, refractory depression, and severe obsessive-compulsive disorder (OCD).

Antidepressant effects. The FDA recently approved DBS under its humanitarian device exemption program for intractable, severe, disabling OCD based on promising results from open and blind trials that stimulated areas such as the internal capsule and adjacent ventral striatum.^20-22 These studies reported that DBS of the caudate nucleus for OCD and subthalamic nucleus for Parkinson’s disease also produced antidepressant effects. Subsequently, trials targeting the subgenual region (Brodmann’s area 25), the ventral capsule/ventral striatum, and nucleus accumbens demonstrated antidepressant effects.^23-27 Pending the results of ongoing pilot trials, large, multi-center studies using different devices and target areas are being planned to clarify the role of DBS for patients with severe, disabling, refractory depression.

Adverse effects of DBS can be:

• surgical-related (eg, seizure, bleeding, infection)
• device-related (eg, lead breakage, malfunction)
• stimulation-related (eg, paresthesia, dysarthria, memory disruption, cognitive changes, psychiatric symptoms).

The most serious risk is intracranial bleeding, which occurs in 2% to 3% of patients. Clearly, the risk-benefit ratio must be carefully considered.

Cost and reimbursement

Cost of treatment and potential for third-party reimbursement are important considerations for any risk-benefit analysis. Many patients who seek neuromodulation treatments will not have insurance or other coverage entitlements.^28-30 Further, newer treatments are not routinely covered by insurance; however, individual case coverage may be allowed and some device manufacturers have programs to assist providers and patients obtain coverage.^28-30 Even ECT, which has long been a covered treatment for major depression, is still considered investigational for other disorders. Thus, it is important to pre-certify with the patient’s health insurance provider before initiating treatment.

Coverage, however, is not the only consideration when weighing cost effectiveness. Economic studies can assist with clinical and ethical decisions relating to treatment choice.³¹ These studies, however, need to be critically evaluated (eg, what costs were included in the analysis). Although direct costs are easier to evaluate, indirect costs—such as the patient’s ability to continue to work while receiving the treatment, caretaker availability during treatment, and whether treatment is an inpatient or outpatient procedure—are more difficult to evaluate and should be discussed with the patient. Because these specialized options have the potential to further benefit patients with depression and other neuropsychiatric disorders, it is essential to balance the pressures of cost containment with the need for more effective and better tolerated treatments.^32-34

Related Resource

• Brunoni AR, Teng CT, Correa C, et al. Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting. Arq Neuropsiquiatr. 2010;68(3):433-451.

Drug Brand Names

• Lithium • Eskalith, Lithobid
• Nortriptyline • Aventyl, Pamelor

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/therapeutic-neuromodulation.html#comments

The brain is an electrochemical organ, and its activity can be modulated for therapeutic purposes by electrical, pharmacologic, or combined approaches. In general, neuromodulation induces electrical current in peripheral or central nervous tissue, which is accomplished by various techniques, including:

• electroconvulsive therapy (ECT)
• vagus nerve stimulation (VNS)
• transcranial magnetic stimulation (TMS)
• deep brain stimulation (DBS).

It is thought that therapeutic benefit occurs by regulating functional disturbances in relevant distributed neural circuits.¹ Depending on the stimulation method, the frequencies chosen may excite or inhibit different or the same areas of the brain in varying patterns. Unlike medication, neuromodulation impacts the brain episodically, which may mitigate adaptation to the therapy’s beneficial effects and avoid systemic adverse effects.

Neuromodulation techniques are categorized based on their risk level as invasive or noninvasive and seizurogenic or nonseizurogenic (Table 1). Although these and other approaches are being considered for various neuropsychiatric disorders (Table 2), the most common application is for severe, treatment-resistant depression. Therefore, this article focuses on FDA-approved neuromodulation treatments for depression, with limited discussion of other indications.

Table 1

Therapeutic neuromodulation: Categorization based on risk

Table 2

Approved and investigational indications of neuromodulation

ECT: Oldest and most effective

ECT has remained the most effective therapeutic neuromodulation technique for more than 7 decades. It is indicated primarily for severe depressive episodes (eg, psychotic, melancholic), particularly in older patients.

ECT delivers electrical current to the CNS that is sufficient to produce a seizure. Under modified conditions, a typical course of 6 to 12 sessions can resolve severe depressive episodes and may also benefit other disorders, such as bipolar mania and acute psychosis. Although ECT is potentially life-saving, its use was markedly curtailed with the advent of effective antidepressants in the 1950s. Multiple factors impede its use, including:

• access and expertise are limited in many areas
• cognition is at least temporarily adversely affected
• relapse rates after acute benefit are high
• cost
• public perception often is negative.

Studies are addressing several of these concerns. For example, the National Institute of Mental Health-sponsored Consortium on Research with ECT (CORE) group is considering how to more effectively maintain acute benefits of ECT. They compared the potential merits of maintenance ECT with maintenance pharmacotherapy (nortriptyline plus lithium) over 6 months. Although the 2 strategies had comparable results, retention rates were <50% and about one-third relapsed in both groups.^2,3 Potential alternative strategies include a more frequent ECT maintenance schedule and/or combining maintenance ECT with medication(s).

Magnetic seizure therapy (MST) and focal electrically administered seizure therapy (FEAST) are attempts to produce similar efficacy and less cognitive disruption compared with ECT.^4,5 Work also continues on electrode placement (eg, bifrontal) and alteration of waveform characteristics (eg, ultra-brief) to maintain or enhance efficacy while minimizing adverse effects.^6,7

Stimulating the vagus nerve

VNS was introduced for treating refractory epilepsy in 1997. In 2005, it became the first FDA-approved implantable device for managing chronic or recurrent treatment-resistant depression.

The vagus nerve is the principal parasympathetic, efferent tract regulating heart rate, intestinal motility, and gastric acid secretion. Information about pain, hunger, and satiety is conveyed by these fibers to the median raphe nucleus and locus coeruleus, brain regions with significant serotonergic and noradrenergic innervation. These neurotransmitters also are believed to play a pivotal role in major depression.

With VNS, a pacemaker-like pulse generator is surgically implanted subcutaneously in the patient’s upper left chest. Wires extend from this device to the left vagus nerve (80% of whose fibers are afferent) located in the neck, to which the pulse generator sends electrical signals every few seconds (Table 3). The right vagus nerve is not used because it provides parasympathetic innervation to the heart. A clinician adjusts stimulation parameters using a computer and a noninvasive handheld device. Common adverse effects include voice alteration or hoarseness, cough, and shortness of breath, which occur during active stimulation because of the proximity of the electrodes to the laryngeal and pharyngeal branches of the vagus nerve. These effects may improve by adjusting stimulation intensity. The device permits a wide range of duty cycles, but preclinical animal studies indicate that >50% activation periods may damage the vagus nerve. If patients become too uncomfortable, they may deactivate the device with a magnet held over the implantation area.

Two open-label studies evaluated VNS to treat major depression. The first involved 10 weeks of stimulation in 59 subjects with chronic or recurrent, nonpsychotic, unipolar or bipolar depression who failed at least 2 adequate antidepressant trials in the current episode.⁸ Stable doses of concomitant antidepressants or mood stabilizers were allowed. After 3 months, 18 (31%) patients responded within an average of 45.5 days, and nearly 15% achieved remission. Response was defined as 50% reduction in baseline Hamilton Depression Rating Scale-28 (HDRS-28) score; remission was defined as HDRS-28 score ≤10. Further, clinical response did not differ between unipolar and bipolar depression patients.

In the second trial, 74 patients with treatment-resistant depression received fixed dose antidepressants and VNS for 3 months, followed by 9 months of flexibly dosed VNS and antidepressants.⁹ At 3 months, response (≥50% reduction in HDRS-28 score) and remission (HDRS-28 score <10) rates were 37% and 17%, respectively, and increased to 53% and 33% at 1 year.

A sham-controlled trial of VNS in 235 depressed patients used similar inclusion and exclusion criteria as in the open-label study by Sackeim et al.^8,10 Two weeks after device implantation, patients were randomized to active treatment (stimulator turned on) or sham control (stimulator left off). At 3 months, the primary outcome measure—response rate based on HDRS-24 score—did not differ significantly between the active and control groups (15% vs 10%, respectively). There was, however, a significantly greater improvement in Inventory of Depressive Symptomatology-Self Report Scale scores with active VNS vs sham VNS.

Patients on sham treatment then were switched to active treatment and both groups were followed for 12 additional months, at which time response and remission rates nearly doubled for both groups.¹¹ In a post-hoc analysis, the same investigators found significant improvement with VNS compared with a naturalistic, matched control group with similar treatment-resistant depression.¹² The FDA considered this adequate to support efficacy and approved the device for chronic or recurrent treatment-resistant depression in an episode not responsive to at least 4 adequate treatment trials with pharmacotherapy or ECT. Perhaps because post-hoc analyses typically are not sufficient to gain FDA approval, most insurance companies do not reimburse for VNS treatment of depression, and VNS is not frequently used for refractory depression.

Table 3

Vagus nerve stimulation treatment parameters

A newer option: TMS

TMS is the most recently FDA-approved therapeutic neuromodulation technique for treating depression. In October 2008, a TMS device became available for patients failing to respond to 1 adequate antidepressant trial during the current episode.

TMS delivers intense, intermittent magnetic pulses produced by an electrical charge into a ferromagnetic coil. The pulse intensity is similar to that produced by MRI. The coil usually is placed on the scalp over the left dorsolateral prefrontal cortex (DLPFC) and pulses are delivered in a rapid, repetitive train, causing neuronal depolarization in a small area of the adjacent cerebral cortex, as well as distal effects in other relevant neural circuits (Table 4). TMS typically is administered on an outpatient basis. A standard treatment course for depression consists of 5 treatment sessions per week for 4 to 8 weeks, depending on symptom severity and how quickly patients respond.

TMS initially was examined in several small, open-label studies that looked at various treatment parameters and stimulation sites. Several sham-controlled studies generally found TMS efficacious and further refined treatment administration. Its role in treating depression—and possibly other psychiatric disorders—has been supported by 2 recent meta-analyses.^13,14

O’Reardon et al¹⁵ conducted the largest double-blind trial of active vs sham TMS (N=301) for moderately treatment-resistant major depression. This study began with a 4- to 6-week, blinded, randomized phase followed by 6 weeks of open-label TMS for initial nonresponders. The third phase reintroduced TMS over 6 months as needed to augment maintenance antidepressants. This trial utilized the most aggressive treatment parameters to date (ie, 10 Hz; 75 4-second trains; 26-second inter-train interval; 120% motor threshold) delivering 3,000 pulses per treatment over an average of 24 sessions. Compared with the sham procedure, patients who received active TMS showed significantly higher response rates on the Montgomery-Åsberg Depression Rating Scale (MADRS) at weeks 4 and 6. Similar results were found for the 17- and 24-item HDRS. At 6 weeks, remission rate—defined as a MADRS score <10—was significantly higher in the active treatment group (14%) compared with the sham procedure (6%). A post-hoc analysis found that the most robust benefit occurred in patients with only 1 failed adequate antidepressant trial (effect size=0.83).¹⁶ This administration protocol was well tolerated, with no deaths or seizures and a low rate of discontinuation because of adverse events (5%).¹⁷ The most common adverse effects were application site pain or discomfort and headaches.

Recently, the second largest (N=190) sham-controlled trial of TMS for treatment-resistant major depression was published.¹⁸ This National Institute of Mental Health-sponsored, multiphase study included an initial 2-week, treatment-free period; 3 weeks of daily treatments over the left DLPFC using the same device and parameters as in the O’Reardon study; and an additional 3 weeks of treatment in patients who were improving. Those not responding to initial treatment were crossed over to open-label active TMS. This study advanced TMS development by:

• using a novel somatosensory system that produced similar sensations with sham and active TMS
• assessing the success of maintaining the blind
• establishing a rigorous clinical rating system
• utilizing MRI-guided adjustment of coil placement in a subset of patients.

The authors concluded that active TMS was significantly better than sham treatment in achieving remission (14% vs 5%). In addition, the raters, treaters, and patients were effectively blinded to the treatment condition. MRI-assisted coil placement found that in 33% of the sample, site placement determined by standardized assessment was over the premotor cortex rather than the prefrontal cortex, so the coil was moved 1 additional cm anteriorly in these patients. Similar to those observed by O’Reardon et al, adverse effects of active TMS were generally mild to moderate, did not differ by treatment condition, and led to a low discontinuation rate (5.5%).

Table 4

Treatment parameters of transcranial magnetic stimulation

Deep brain stimulation

DBS is a “functional neurosurgical” procedure that delivers electrical current directly to specific areas within the brain.¹⁹ Its mechanism of action remains uncertain; depolarization blockade, synaptic inhibition, and “neural jamming” are leading hypotheses. In contrast to conventional ablative surgeries, DBS is reversible and adjustable. Implantation involves positioning pacemaker-like battery devices subcutaneously in the left and right upper chest. Electrodes attached to wires are run subcutaneously behind the ears and, with stereotactic guidance, placed through burr holes in the skull into specific CNS areas implicated in the pathophysiology of conditions such as Parkinson’s disease, refractory depression, and severe obsessive-compulsive disorder (OCD).

Antidepressant effects. The FDA recently approved DBS under its humanitarian device exemption program for intractable, severe, disabling OCD based on promising results from open and blind trials that stimulated areas such as the internal capsule and adjacent ventral striatum.^20-22 These studies reported that DBS of the caudate nucleus for OCD and subthalamic nucleus for Parkinson’s disease also produced antidepressant effects. Subsequently, trials targeting the subgenual region (Brodmann’s area 25), the ventral capsule/ventral striatum, and nucleus accumbens demonstrated antidepressant effects.^23-27 Pending the results of ongoing pilot trials, large, multi-center studies using different devices and target areas are being planned to clarify the role of DBS for patients with severe, disabling, refractory depression.

Adverse effects of DBS can be:

• surgical-related (eg, seizure, bleeding, infection)
• device-related (eg, lead breakage, malfunction)
• stimulation-related (eg, paresthesia, dysarthria, memory disruption, cognitive changes, psychiatric symptoms).

The most serious risk is intracranial bleeding, which occurs in 2% to 3% of patients. Clearly, the risk-benefit ratio must be carefully considered.

Cost and reimbursement

Cost of treatment and potential for third-party reimbursement are important considerations for any risk-benefit analysis. Many patients who seek neuromodulation treatments will not have insurance or other coverage entitlements.^28-30 Further, newer treatments are not routinely covered by insurance; however, individual case coverage may be allowed and some device manufacturers have programs to assist providers and patients obtain coverage.^28-30 Even ECT, which has long been a covered treatment for major depression, is still considered investigational for other disorders. Thus, it is important to pre-certify with the patient’s health insurance provider before initiating treatment.

Coverage, however, is not the only consideration when weighing cost effectiveness. Economic studies can assist with clinical and ethical decisions relating to treatment choice.³¹ These studies, however, need to be critically evaluated (eg, what costs were included in the analysis). Although direct costs are easier to evaluate, indirect costs—such as the patient’s ability to continue to work while receiving the treatment, caretaker availability during treatment, and whether treatment is an inpatient or outpatient procedure—are more difficult to evaluate and should be discussed with the patient. Because these specialized options have the potential to further benefit patients with depression and other neuropsychiatric disorders, it is essential to balance the pressures of cost containment with the need for more effective and better tolerated treatments.^32-34

Related Resource

• Brunoni AR, Teng CT, Correa C, et al. Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting. Arq Neuropsiquiatr. 2010;68(3):433-451.

Drug Brand Names

• Lithium • Eskalith, Lithobid
• Nortriptyline • Aventyl, Pamelor

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/depression-treatment-for-women-with.html#comments

Psychological distress among patients with breast cancer is common and is linked to worse clinical outcomes. Depressive and anxiety symptoms affect up to 40% of breast cancer patients,¹ and depression is associated with a higher relative risk of mortality in individuals with breast cancer.² Psychotropic medications and psychotherapy used to treat depression in patients without carcinoma also are appropriate and effective for breast cancer patients. However, some patients present distinct challenges to standard treatment. For example, growing evidence suggests that some selective serotonin reuptake inhibitors (SSRIs) may reduce the effectiveness of tamoxifen, a chemotherapeutic agent. This article discusses challenges in diagnosing and treating depression in breast cancer patients and reviews evidence supporting appropriate psychiatric care.

Increased vulnerability

In 10% to 30% of women, a breast cancer diagnosis may lead to increased vulnerability to depressive disorders, including adjustment disorders with depressed mood, major depressive disorder (MDD), and mood disorders related to general medical conditions.^3,4 The risk of developing a depressive disorder is highest in the year after receiving the breast cancer diagnosis.⁴

A woman’s risk of developing a depressive disorder may depend on the type of cancer treatment she receives. For example, breast asymmetry is common after breast conserving surgery. Waljee et al⁵ found that women with breast asymmetry had increased fears of cancer recurrence and more feelings of self-consciousness. More pronounced asymmetry led to a higher incidence of depressive symptoms. However, among 90 patients undergoing bilateral prophylactic mastectomy, the rate of depression had not changed 1 year after the procedure.⁶ Chemotherapy, particularly at high doses, is a risk factor for depression.^4,7,8

Self-blame for developing breast cancer can affect mood. In 2007, Friedman et al⁹ determined that higher levels of self-blame correlated with higher levels of depression and decreased quality of life. Women often blamed themselves for various reasons, including:

• poor coping skills
• anxiety about their health and treatments
• inability to express emotions
• delays in medical consultation.

Exacerbated symptoms and side effects. Women with depression often experience increased side effects from cancer treatments, and the subjective experience of these effects—including hot flashes, cognitive impairment, pain, and sexual dysfunction—likely is intensified.⁴ Somatic symptoms of depression may be exacerbated by cancer treatment side effects or mistaken for effects of the treatment. When somatic symptoms of depression are mistaken for treatment side effects, depression—and the opportunity to treat it—can be overlooked.¹⁰

Depression may be a risk factor for poor adherence to cancer treatment. In a quantitative review of studies correlating depression and medical treatment noncompliance, DiMatteo et al¹¹ determined that compared with nondepressed patients, those with depression were 3 times more likely to not adhere to treatment recommendations; this review was not limited to cancer patients. Depressive symptoms—notably poor concentration and amotivation—can create the impression that a patient is poorly adherent. Women with comorbid depression and breast cancer may have difficulty understanding treatment recommendations or remembering daily treatment goals.⁴

Appropriate screening tools

Factors that may increase a breast cancer patient’s risk for developing a psychiatric disorder are listed in Table 1.¹⁰ Many depression screening tools are available; below we describe 3 commonly used for patients with breast cancer.

The National Comprehensive Cancer Center Distress Thermometer allows patients to rate their overall distress level over the past week on a scale from 0 to 10, using a visual analogue.¹² The Distress Thermometer has been validated for several cancer populations and in different parts of the world. A score of 7 has both good sensitivity and specificity for detecting depression in breast cancer patients. Consider a complete psychiatric evaluation for patients with scores ≥7.¹³

The Profile of Mood States questionnaire¹⁴ is a reliable, valid 65-item questionnaire often used in studies of mood dysregulation and breast cancer. Subscales include depression-dejection, tension-anxiety, anger-hostility, confusion-bewilderment, vigor-activity, and fatigue-inertia. Using a 5-point Likert scale, patients rate their symptoms over the past week. Subscale scores are then added to a total mood disturbance score.^14,15

The Hospital Anxiety and Depression Scale (HADS) is a sensitive, reliable 14-item scale that is commonly used to study depression and anxiety in patients with breast cancer.¹⁶ HADS includes two 7-item subscales—anxiety and depression—and answers are scored on a 4-point Likert scale. Patients are asked to respond quickly and avoid thinking too long about their answers.

Table 1

Risk factors for psychiatric distress related to breast cancer

Psychotherapeutic options

Behavioral therapies can diminish symptoms of depression, according to a review of studies and practice guidelines on managing depression in cancer patients.¹⁷ Group interventions, in particular, can be valuable. Anderson et al¹⁸ found that group cohesion, member connectedness, and more sessions correlated with decreased psychological distress.

Psychoeducation aims to provide medical information and discuss cancer’s causes, prognosis, and treatment strategies. Group settings can help improve communication and problem-solving skills. In a randomized controlled trial (RCT) of 203 women with breast cancer, psychoeducational group treatment reduced depression, anger, and fatigue.¹⁹

Cognitive-behavioral therapy (CBT) helps patients identify and restructure negative thoughts and increase positive, adaptive behaviors. Hunter et al²⁰ noted significant improvement in depressed mood, anxiety, and sleep in 17 women experiencing menopausal symptoms who received group CBT after completing breast cancer treatment. In 1 study, 124 patients with metastatic breast cancer who received 8 weekly sessions of group CBT reported reduced depression and mood disturbance and improved self-esteem compared with a no-therapy control group.²¹

Supportive-expressive therapy (SET) is a manual-based therapy that focuses on increasing social support, improving symptom control, and enhancing communication between the patient and treatment team. Affective expression helps lead the therapist to issues that should be addressed. Evidence on the effectiveness of SET for patients with breast cancer is mixed. A study of 357 women with breast cancer who were randomly assigned to 12-week group SET or an educational control condition found no evidence that SET reduced distress.²² However, a trial of 485 women with advanced breast cancer who were randomly assigned to group SET plus relaxation therapy or relaxation therapy alone showed that SET improved quality of life, including protection against depression.²³

Mindfulness-based stress reduction (MBSR) is a standardized form of meditation and yoga. Clinicians teach patients visualization, breathing exercises, and meditation to help them become aware of the body’s reaction to stress and how to regulate it. In an RCT of 84 female breast cancer survivors, a 6-week MBSR program diminished depressive symptoms, improved physical functioning, and reduced fear of cancer recurrence.²⁴

Evidence for antidepressants

SSRIs. Expert consensus guidelines on treating depression in women recommend an SSRI as a first-line agent.²⁵ In RCTs, fluoxetine, paroxetine, and sertraline were more effective than placebo in treating depression and related symptoms specifically in women with breast cancer (Table 2).^26-28

The interaction between SSRIs and chemotherapy agents is a concern. Tamoxifen decreases the rate of death from breast cancer in hormone receptor positive breast cancers.²⁹ Endoxifen, a potent anti-estrogen, is an active metabolite of tamoxifen via cytochrome P450 (CYP) 2D6. Goetz et al³⁰ demonstrated that women with decreased or inhibited metabolism via CYP2D6 had significantly shorter times to breast cancer recurrence, compared with women with extensive CYP2D6 metabolism.

SSRIs can varyingly inhibit CYP2D6. In a prospective trial of 158 breast cancer patients receiving tamoxifen, paroxetine and fluoxetine were found to be strong inhibitors of CYP2D6 and led to low levels of endoxifen.³¹ In contrast, weaker inhibitors, including sertraline and citalopram, led to intermediate levels of endoxifen. In a retrospective cohort study, Kelly et al³² demonstrated that women treated with paroxetine, in combination with tamoxifen, had an increased risk of death compared with women treated with other SSRIs or venlafaxine and tamoxifen. They estimated that paroxetine use in women treated with tamoxifen would lead to 1 additional breast cancer death per 20 women within 5 years of discontinuing tamoxifen.

According to American Psychiatric Association practice guidelines for treatment of MDD, depressed breast cancer patients who receive tamoxifen generally should be treated with an antidepressant that has minimal effect on CYP2D6 metabolism, such as citalopram, escitalopram, venlafaxine, or desvenlafaxine.³³

Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used to treat depressive disorders. In addition, venlafaxine may be helpful in treating post-mastectomy pain syndrome. Approximately one-half of patients who undergo mastectomy or breast reconstruction may experience a postoperative pain syndrome.³⁴ The most common symptom is a burning, stabbing pain in the axilla, arm, and chest wall of the affected side. This pain is worsened by movement and is poorly responsive to opioids.³⁵

In a 10-week RCT of 13 patients with neuropathic pain after breast cancer treatment, venlafaxine significantly improved pain relief compared with placebo, although the drug did not affect depression or anxiety.³⁶ In a study of 100 patients given venlafaxine or placebo for 2 weeks starting the night before undergoing partial or radical mastectomy with axillary dissection, those receiving venlafaxine had a significantly lower incidence of pain in the chest wall, arm, and axillary region, and scores of pain with movement were decreased.³⁷ There was no difference in opioid usage between groups.

Tricyclic antidepressants have been demonstrated to be effective in breast cancer patients. Side effects—notably anticholinergic effects—limit their use as antidepressants, especially when compared with SSRI treatment. In a study that randomly assigned 179 women with breast cancer to paroxetine, 20 to 40 mg/d, or amitriptyline, 75 to 150 mg/d, anticholinergic effects were almost twice as frequent in the amitriptyline group (19%) compared with paroxetine (11%).³⁸ In a 4-week double-blind, placebo-controlled crossover trial of 15 breast cancer patients, amitriptyline significantly relieved neuropathic pain, but its adverse effects made most patients unwilling to use the medication regularly.³⁹

Table 2

Evidence supporting SSRI use in patients with breast cancer*

Related Resources

• American Cancer Society. www.cancer.org.
• National Comprehensive Cancer network. www.nccn.org.

Drug Brand Names

• Amitripyline • Elavil
• Citalopram • Celexa
• Desvenlafaxine • Pristiq
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Paroxetine • Paxil
• Sertraline • Zoloft
• Tamoxifen • Nolvadex
• Venlafaxine • Effexor

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/depression-treatment-for-women-with.html#comments

Psychological distress among patients with breast cancer is common and is linked to worse clinical outcomes. Depressive and anxiety symptoms affect up to 40% of breast cancer patients,¹ and depression is associated with a higher relative risk of mortality in individuals with breast cancer.² Psychotropic medications and psychotherapy used to treat depression in patients without carcinoma also are appropriate and effective for breast cancer patients. However, some patients present distinct challenges to standard treatment. For example, growing evidence suggests that some selective serotonin reuptake inhibitors (SSRIs) may reduce the effectiveness of tamoxifen, a chemotherapeutic agent. This article discusses challenges in diagnosing and treating depression in breast cancer patients and reviews evidence supporting appropriate psychiatric care.

Increased vulnerability

In 10% to 30% of women, a breast cancer diagnosis may lead to increased vulnerability to depressive disorders, including adjustment disorders with depressed mood, major depressive disorder (MDD), and mood disorders related to general medical conditions.^3,4 The risk of developing a depressive disorder is highest in the year after receiving the breast cancer diagnosis.⁴

A woman’s risk of developing a depressive disorder may depend on the type of cancer treatment she receives. For example, breast asymmetry is common after breast conserving surgery. Waljee et al⁵ found that women with breast asymmetry had increased fears of cancer recurrence and more feelings of self-consciousness. More pronounced asymmetry led to a higher incidence of depressive symptoms. However, among 90 patients undergoing bilateral prophylactic mastectomy, the rate of depression had not changed 1 year after the procedure.⁶ Chemotherapy, particularly at high doses, is a risk factor for depression.^4,7,8

Self-blame for developing breast cancer can affect mood. In 2007, Friedman et al⁹ determined that higher levels of self-blame correlated with higher levels of depression and decreased quality of life. Women often blamed themselves for various reasons, including:

• poor coping skills
• anxiety about their health and treatments
• inability to express emotions
• delays in medical consultation.

Exacerbated symptoms and side effects. Women with depression often experience increased side effects from cancer treatments, and the subjective experience of these effects—including hot flashes, cognitive impairment, pain, and sexual dysfunction—likely is intensified.⁴ Somatic symptoms of depression may be exacerbated by cancer treatment side effects or mistaken for effects of the treatment. When somatic symptoms of depression are mistaken for treatment side effects, depression—and the opportunity to treat it—can be overlooked.¹⁰

Depression may be a risk factor for poor adherence to cancer treatment. In a quantitative review of studies correlating depression and medical treatment noncompliance, DiMatteo et al¹¹ determined that compared with nondepressed patients, those with depression were 3 times more likely to not adhere to treatment recommendations; this review was not limited to cancer patients. Depressive symptoms—notably poor concentration and amotivation—can create the impression that a patient is poorly adherent. Women with comorbid depression and breast cancer may have difficulty understanding treatment recommendations or remembering daily treatment goals.⁴

Appropriate screening tools

Factors that may increase a breast cancer patient’s risk for developing a psychiatric disorder are listed in Table 1.¹⁰ Many depression screening tools are available; below we describe 3 commonly used for patients with breast cancer.

The National Comprehensive Cancer Center Distress Thermometer allows patients to rate their overall distress level over the past week on a scale from 0 to 10, using a visual analogue.¹² The Distress Thermometer has been validated for several cancer populations and in different parts of the world. A score of 7 has both good sensitivity and specificity for detecting depression in breast cancer patients. Consider a complete psychiatric evaluation for patients with scores ≥7.¹³

The Profile of Mood States questionnaire¹⁴ is a reliable, valid 65-item questionnaire often used in studies of mood dysregulation and breast cancer. Subscales include depression-dejection, tension-anxiety, anger-hostility, confusion-bewilderment, vigor-activity, and fatigue-inertia. Using a 5-point Likert scale, patients rate their symptoms over the past week. Subscale scores are then added to a total mood disturbance score.^14,15

The Hospital Anxiety and Depression Scale (HADS) is a sensitive, reliable 14-item scale that is commonly used to study depression and anxiety in patients with breast cancer.¹⁶ HADS includes two 7-item subscales—anxiety and depression—and answers are scored on a 4-point Likert scale. Patients are asked to respond quickly and avoid thinking too long about their answers.

Table 1

Risk factors for psychiatric distress related to breast cancer

Psychotherapeutic options

Behavioral therapies can diminish symptoms of depression, according to a review of studies and practice guidelines on managing depression in cancer patients.¹⁷ Group interventions, in particular, can be valuable. Anderson et al¹⁸ found that group cohesion, member connectedness, and more sessions correlated with decreased psychological distress.

Psychoeducation aims to provide medical information and discuss cancer’s causes, prognosis, and treatment strategies. Group settings can help improve communication and problem-solving skills. In a randomized controlled trial (RCT) of 203 women with breast cancer, psychoeducational group treatment reduced depression, anger, and fatigue.¹⁹

Cognitive-behavioral therapy (CBT) helps patients identify and restructure negative thoughts and increase positive, adaptive behaviors. Hunter et al²⁰ noted significant improvement in depressed mood, anxiety, and sleep in 17 women experiencing menopausal symptoms who received group CBT after completing breast cancer treatment. In 1 study, 124 patients with metastatic breast cancer who received 8 weekly sessions of group CBT reported reduced depression and mood disturbance and improved self-esteem compared with a no-therapy control group.²¹

Supportive-expressive therapy (SET) is a manual-based therapy that focuses on increasing social support, improving symptom control, and enhancing communication between the patient and treatment team. Affective expression helps lead the therapist to issues that should be addressed. Evidence on the effectiveness of SET for patients with breast cancer is mixed. A study of 357 women with breast cancer who were randomly assigned to 12-week group SET or an educational control condition found no evidence that SET reduced distress.²² However, a trial of 485 women with advanced breast cancer who were randomly assigned to group SET plus relaxation therapy or relaxation therapy alone showed that SET improved quality of life, including protection against depression.²³

Mindfulness-based stress reduction (MBSR) is a standardized form of meditation and yoga. Clinicians teach patients visualization, breathing exercises, and meditation to help them become aware of the body’s reaction to stress and how to regulate it. In an RCT of 84 female breast cancer survivors, a 6-week MBSR program diminished depressive symptoms, improved physical functioning, and reduced fear of cancer recurrence.²⁴

Evidence for antidepressants

SSRIs. Expert consensus guidelines on treating depression in women recommend an SSRI as a first-line agent.²⁵ In RCTs, fluoxetine, paroxetine, and sertraline were more effective than placebo in treating depression and related symptoms specifically in women with breast cancer (Table 2).^26-28

The interaction between SSRIs and chemotherapy agents is a concern. Tamoxifen decreases the rate of death from breast cancer in hormone receptor positive breast cancers.²⁹ Endoxifen, a potent anti-estrogen, is an active metabolite of tamoxifen via cytochrome P450 (CYP) 2D6. Goetz et al³⁰ demonstrated that women with decreased or inhibited metabolism via CYP2D6 had significantly shorter times to breast cancer recurrence, compared with women with extensive CYP2D6 metabolism.

SSRIs can varyingly inhibit CYP2D6. In a prospective trial of 158 breast cancer patients receiving tamoxifen, paroxetine and fluoxetine were found to be strong inhibitors of CYP2D6 and led to low levels of endoxifen.³¹ In contrast, weaker inhibitors, including sertraline and citalopram, led to intermediate levels of endoxifen. In a retrospective cohort study, Kelly et al³² demonstrated that women treated with paroxetine, in combination with tamoxifen, had an increased risk of death compared with women treated with other SSRIs or venlafaxine and tamoxifen. They estimated that paroxetine use in women treated with tamoxifen would lead to 1 additional breast cancer death per 20 women within 5 years of discontinuing tamoxifen.

According to American Psychiatric Association practice guidelines for treatment of MDD, depressed breast cancer patients who receive tamoxifen generally should be treated with an antidepressant that has minimal effect on CYP2D6 metabolism, such as citalopram, escitalopram, venlafaxine, or desvenlafaxine.³³

Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used to treat depressive disorders. In addition, venlafaxine may be helpful in treating post-mastectomy pain syndrome. Approximately one-half of patients who undergo mastectomy or breast reconstruction may experience a postoperative pain syndrome.³⁴ The most common symptom is a burning, stabbing pain in the axilla, arm, and chest wall of the affected side. This pain is worsened by movement and is poorly responsive to opioids.³⁵

In a 10-week RCT of 13 patients with neuropathic pain after breast cancer treatment, venlafaxine significantly improved pain relief compared with placebo, although the drug did not affect depression or anxiety.³⁶ In a study of 100 patients given venlafaxine or placebo for 2 weeks starting the night before undergoing partial or radical mastectomy with axillary dissection, those receiving venlafaxine had a significantly lower incidence of pain in the chest wall, arm, and axillary region, and scores of pain with movement were decreased.³⁷ There was no difference in opioid usage between groups.

Tricyclic antidepressants have been demonstrated to be effective in breast cancer patients. Side effects—notably anticholinergic effects—limit their use as antidepressants, especially when compared with SSRI treatment. In a study that randomly assigned 179 women with breast cancer to paroxetine, 20 to 40 mg/d, or amitriptyline, 75 to 150 mg/d, anticholinergic effects were almost twice as frequent in the amitriptyline group (19%) compared with paroxetine (11%).³⁸ In a 4-week double-blind, placebo-controlled crossover trial of 15 breast cancer patients, amitriptyline significantly relieved neuropathic pain, but its adverse effects made most patients unwilling to use the medication regularly.³⁹

Table 2

Evidence supporting SSRI use in patients with breast cancer*

Related Resources

• American Cancer Society. www.cancer.org.
• National Comprehensive Cancer network. www.nccn.org.

Drug Brand Names

• Amitripyline • Elavil
• Citalopram • Celexa
• Desvenlafaxine • Pristiq
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Paroxetine • Paxil
• Sertraline • Zoloft
• Tamoxifen • Nolvadex
• Venlafaxine • Effexor

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/depression-treatment-for-women-with.html#comments

Psychological distress among patients with breast cancer is common and is linked to worse clinical outcomes. Depressive and anxiety symptoms affect up to 40% of breast cancer patients,¹ and depression is associated with a higher relative risk of mortality in individuals with breast cancer.² Psychotropic medications and psychotherapy used to treat depression in patients without carcinoma also are appropriate and effective for breast cancer patients. However, some patients present distinct challenges to standard treatment. For example, growing evidence suggests that some selective serotonin reuptake inhibitors (SSRIs) may reduce the effectiveness of tamoxifen, a chemotherapeutic agent. This article discusses challenges in diagnosing and treating depression in breast cancer patients and reviews evidence supporting appropriate psychiatric care.

Increased vulnerability

In 10% to 30% of women, a breast cancer diagnosis may lead to increased vulnerability to depressive disorders, including adjustment disorders with depressed mood, major depressive disorder (MDD), and mood disorders related to general medical conditions.^3,4 The risk of developing a depressive disorder is highest in the year after receiving the breast cancer diagnosis.⁴

A woman’s risk of developing a depressive disorder may depend on the type of cancer treatment she receives. For example, breast asymmetry is common after breast conserving surgery. Waljee et al⁵ found that women with breast asymmetry had increased fears of cancer recurrence and more feelings of self-consciousness. More pronounced asymmetry led to a higher incidence of depressive symptoms. However, among 90 patients undergoing bilateral prophylactic mastectomy, the rate of depression had not changed 1 year after the procedure.⁶ Chemotherapy, particularly at high doses, is a risk factor for depression.^4,7,8

Self-blame for developing breast cancer can affect mood. In 2007, Friedman et al⁹ determined that higher levels of self-blame correlated with higher levels of depression and decreased quality of life. Women often blamed themselves for various reasons, including:

• poor coping skills
• anxiety about their health and treatments
• inability to express emotions
• delays in medical consultation.

Exacerbated symptoms and side effects. Women with depression often experience increased side effects from cancer treatments, and the subjective experience of these effects—including hot flashes, cognitive impairment, pain, and sexual dysfunction—likely is intensified.⁴ Somatic symptoms of depression may be exacerbated by cancer treatment side effects or mistaken for effects of the treatment. When somatic symptoms of depression are mistaken for treatment side effects, depression—and the opportunity to treat it—can be overlooked.¹⁰

Depression may be a risk factor for poor adherence to cancer treatment. In a quantitative review of studies correlating depression and medical treatment noncompliance, DiMatteo et al¹¹ determined that compared with nondepressed patients, those with depression were 3 times more likely to not adhere to treatment recommendations; this review was not limited to cancer patients. Depressive symptoms—notably poor concentration and amotivation—can create the impression that a patient is poorly adherent. Women with comorbid depression and breast cancer may have difficulty understanding treatment recommendations or remembering daily treatment goals.⁴

Appropriate screening tools

Factors that may increase a breast cancer patient’s risk for developing a psychiatric disorder are listed in Table 1.¹⁰ Many depression screening tools are available; below we describe 3 commonly used for patients with breast cancer.

The National Comprehensive Cancer Center Distress Thermometer allows patients to rate their overall distress level over the past week on a scale from 0 to 10, using a visual analogue.¹² The Distress Thermometer has been validated for several cancer populations and in different parts of the world. A score of 7 has both good sensitivity and specificity for detecting depression in breast cancer patients. Consider a complete psychiatric evaluation for patients with scores ≥7.¹³

The Profile of Mood States questionnaire¹⁴ is a reliable, valid 65-item questionnaire often used in studies of mood dysregulation and breast cancer. Subscales include depression-dejection, tension-anxiety, anger-hostility, confusion-bewilderment, vigor-activity, and fatigue-inertia. Using a 5-point Likert scale, patients rate their symptoms over the past week. Subscale scores are then added to a total mood disturbance score.^14,15

The Hospital Anxiety and Depression Scale (HADS) is a sensitive, reliable 14-item scale that is commonly used to study depression and anxiety in patients with breast cancer.¹⁶ HADS includes two 7-item subscales—anxiety and depression—and answers are scored on a 4-point Likert scale. Patients are asked to respond quickly and avoid thinking too long about their answers.

Table 1

Risk factors for psychiatric distress related to breast cancer

Psychotherapeutic options

Behavioral therapies can diminish symptoms of depression, according to a review of studies and practice guidelines on managing depression in cancer patients.¹⁷ Group interventions, in particular, can be valuable. Anderson et al¹⁸ found that group cohesion, member connectedness, and more sessions correlated with decreased psychological distress.

Psychoeducation aims to provide medical information and discuss cancer’s causes, prognosis, and treatment strategies. Group settings can help improve communication and problem-solving skills. In a randomized controlled trial (RCT) of 203 women with breast cancer, psychoeducational group treatment reduced depression, anger, and fatigue.¹⁹

Cognitive-behavioral therapy (CBT) helps patients identify and restructure negative thoughts and increase positive, adaptive behaviors. Hunter et al²⁰ noted significant improvement in depressed mood, anxiety, and sleep in 17 women experiencing menopausal symptoms who received group CBT after completing breast cancer treatment. In 1 study, 124 patients with metastatic breast cancer who received 8 weekly sessions of group CBT reported reduced depression and mood disturbance and improved self-esteem compared with a no-therapy control group.²¹

Supportive-expressive therapy (SET) is a manual-based therapy that focuses on increasing social support, improving symptom control, and enhancing communication between the patient and treatment team. Affective expression helps lead the therapist to issues that should be addressed. Evidence on the effectiveness of SET for patients with breast cancer is mixed. A study of 357 women with breast cancer who were randomly assigned to 12-week group SET or an educational control condition found no evidence that SET reduced distress.²² However, a trial of 485 women with advanced breast cancer who were randomly assigned to group SET plus relaxation therapy or relaxation therapy alone showed that SET improved quality of life, including protection against depression.²³

Mindfulness-based stress reduction (MBSR) is a standardized form of meditation and yoga. Clinicians teach patients visualization, breathing exercises, and meditation to help them become aware of the body’s reaction to stress and how to regulate it. In an RCT of 84 female breast cancer survivors, a 6-week MBSR program diminished depressive symptoms, improved physical functioning, and reduced fear of cancer recurrence.²⁴

Evidence for antidepressants

SSRIs. Expert consensus guidelines on treating depression in women recommend an SSRI as a first-line agent.²⁵ In RCTs, fluoxetine, paroxetine, and sertraline were more effective than placebo in treating depression and related symptoms specifically in women with breast cancer (Table 2).^26-28

The interaction between SSRIs and chemotherapy agents is a concern. Tamoxifen decreases the rate of death from breast cancer in hormone receptor positive breast cancers.²⁹ Endoxifen, a potent anti-estrogen, is an active metabolite of tamoxifen via cytochrome P450 (CYP) 2D6. Goetz et al³⁰ demonstrated that women with decreased or inhibited metabolism via CYP2D6 had significantly shorter times to breast cancer recurrence, compared with women with extensive CYP2D6 metabolism.

SSRIs can varyingly inhibit CYP2D6. In a prospective trial of 158 breast cancer patients receiving tamoxifen, paroxetine and fluoxetine were found to be strong inhibitors of CYP2D6 and led to low levels of endoxifen.³¹ In contrast, weaker inhibitors, including sertraline and citalopram, led to intermediate levels of endoxifen. In a retrospective cohort study, Kelly et al³² demonstrated that women treated with paroxetine, in combination with tamoxifen, had an increased risk of death compared with women treated with other SSRIs or venlafaxine and tamoxifen. They estimated that paroxetine use in women treated with tamoxifen would lead to 1 additional breast cancer death per 20 women within 5 years of discontinuing tamoxifen.

According to American Psychiatric Association practice guidelines for treatment of MDD, depressed breast cancer patients who receive tamoxifen generally should be treated with an antidepressant that has minimal effect on CYP2D6 metabolism, such as citalopram, escitalopram, venlafaxine, or desvenlafaxine.³³

Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used to treat depressive disorders. In addition, venlafaxine may be helpful in treating post-mastectomy pain syndrome. Approximately one-half of patients who undergo mastectomy or breast reconstruction may experience a postoperative pain syndrome.³⁴ The most common symptom is a burning, stabbing pain in the axilla, arm, and chest wall of the affected side. This pain is worsened by movement and is poorly responsive to opioids.³⁵

In a 10-week RCT of 13 patients with neuropathic pain after breast cancer treatment, venlafaxine significantly improved pain relief compared with placebo, although the drug did not affect depression or anxiety.³⁶ In a study of 100 patients given venlafaxine or placebo for 2 weeks starting the night before undergoing partial or radical mastectomy with axillary dissection, those receiving venlafaxine had a significantly lower incidence of pain in the chest wall, arm, and axillary region, and scores of pain with movement were decreased.³⁷ There was no difference in opioid usage between groups.

Tricyclic antidepressants have been demonstrated to be effective in breast cancer patients. Side effects—notably anticholinergic effects—limit their use as antidepressants, especially when compared with SSRI treatment. In a study that randomly assigned 179 women with breast cancer to paroxetine, 20 to 40 mg/d, or amitriptyline, 75 to 150 mg/d, anticholinergic effects were almost twice as frequent in the amitriptyline group (19%) compared with paroxetine (11%).³⁸ In a 4-week double-blind, placebo-controlled crossover trial of 15 breast cancer patients, amitriptyline significantly relieved neuropathic pain, but its adverse effects made most patients unwilling to use the medication regularly.³⁹

Table 2

Evidence supporting SSRI use in patients with breast cancer*

Related Resources

• American Cancer Society. www.cancer.org.
• National Comprehensive Cancer network. www.nccn.org.

Drug Brand Names

• Amitripyline • Elavil
• Citalopram • Celexa
• Desvenlafaxine • Pristiq
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Paroxetine • Paxil
• Sertraline • Zoloft
• Tamoxifen • Nolvadex
• Venlafaxine • Effexor

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/parricide-characteristics-of-sons-and.html#comments

Mr. B, age 37, is single and lives with his elderly mother. Since being diagnosed with schizophrenia in his early 20s, he has been intermittently compliant with antipsychotic therapy. When unmedicated, Mr. B develops paranoid delusions and becomes preoccupied with the idea that his mother is plotting to kill him. He has been hospitalized twice in the last 5 years for physical aggression toward his mother. In the last 10 years, Mr. B has been placed in several group homes, but when he takes his medications, he is able to convince his mother to allow him to live with her.

During his most recent stay in his mother’s home, Mr. B again stops taking his psychotropic medications and decompensates. His mother becomes concerned about her son’s paranoid behavior—such as trying to listen in on her telephone conversations and smelling his food before he eats it—and considers having her son involuntarily committed. One day, after she prepares Mr. B a sandwich, he decides the meat is poisoned. When his mother tries to convince him to eat the sandwich, Mr. B becomes enraged and stabs her 54 times with a kitchen knife.

Mr. B is arrested without resistance. He is adjudicated incompetent to stand trial and is restored to competency within 3 months. Mr. B is found not guilty by reason of insanity (NGRI) and is civilly committed to a state psychiatric facility.

Parricide—killing one’s parents—once was referred to as “the schizophrenic crime,”¹ but is now recognized as being more complex.² In the United States, parricides accounted for 2% of all homicides from 1976 to 1998,³ which is consistent with studies from France⁴ and the United Kingdom.⁵ Parricide’s scandalous nature has long attracted the public’s fascination (see this article at CurrentPsychiatry.com).

This article primarily focuses on the interplay of the diagnostic and demographic factors seen in adults who kill their biological parents but briefly notes differences seen in juvenile perpetrators and those who kill their stepparents. Knowledge of these characteristics can help clinicians identify and more safely manage patients who may be at risk of harming their parents.

Box

A limited evidence base

The common themes found in the literature on parricide should be interpreted cautiously because of the limitations of this research. The number of individuals assessed in these studies often is small, which limits the statistical power of the findings. Studies often are conducted in forensic hospitals, which excludes those who are imprisoned or commit suicide following the acts. Finally, most individuals studied were diagnosed with a psychiatric disorder after the crime, which makes it difficult to distinguish the primary illness from the crime’s effect on a person’s mental state. Additionally, some individuals may be tempted to exaggerate or feign psychiatric symptoms in an effort to be found NGRI or granted leniency during sentencing. Despite these limitations, several conclusions can be drawn from these investigations.

The sex of the victims and perpetrators needs to be carefully considered when reviewing characteristics of those who commit parricide. Killing a mother is matricide, and killing a father is patricide.

Sons who kill their parents

Men are more likely to kill their parents than women.^6-9 In a study of 5,488 cases of parricide in the United States, 4,738 (86%) of perpetrators were male.³ Common characteristics of men who commit parricide are listed in Table 1.^5,8,10-14

Matricide by sons. Although sons kill their fathers more often than their mothers,¹⁵ authors writing about parricide commonly focus on men who commit matricide. Wertham described sons who kill their mothers in terms of the “Orestes Complex,” which refers to ambivalent feelings toward the mother that ultimately manifest in homicidal rage. He noted that many matricides are committed with excessive force, occur in the bedroom, and are precipitated by trivial reasons. Wertham stated that these crimes represent the son’s unconscious hatred for his mother superimposed on sexual desire for her.¹⁶ Sigmund Freud argued that matricide served as a displacement defense against incestuous impulses.¹⁷

In 5 studies that looked at sons who killed their mothers (n=13 to 58),^5,10-13 most of which examined men residing in forensic hospitals after the crime, perpetrators were noted to be immature, dependent, and passive. In a study of 16 men with schizophrenia who committed matricide, subjects perceived themselves as “weak, small, inadequate, hopeless, doubtful about sexual identity, dependent, and unable to accept a separate, adult male role.”¹¹ Mothers generally were domineering, demanding, and possessive.

Based on our literature review, most men who committed matricide had a schizophrenia diagnosis (weighted mean 72%, range 50% to 100%); other diagnoses included depression and personality disorders. Many men were experiencing psychosis shortly before the crime, and their acts were influenced by persecutory delusions and/or auditory hallucinations. Approximately one-quarter of sons killed their mothers for altruistic reasons, such as to relieve actual or perceived suffering.

Nearly all men in these 5 studies were single and lived with their mothers before killing them, and many of the perpetrators’ fathers were absent. Mothers often were the only victims of their sons’ violent acts. In addition to delusional beliefs, sons were motivated to kill their mothers for various reasons, including threatened separation or minor arguments (eg, over food or money). Many of these homicides took place in the home. Sharp or blunt objects were the most common weapons, but guns and strangulation/asphyxiation also were used. Approximately one-half of the men used excessive violence; for example, 1 victim had 177 stab wounds. After the crimes, the perpetrators generally expressed remorse or relief.

Patricide by sons. Psychoanalysts may consider the Oedipal Complex to be the primary impetus for a son to commit patricide. By eliminating his father the son gains possession of his mother.¹⁸ Three studies looked at sons who killed their fathers; 2 examined 10 perpetrators residing in a forensic hospital after the crimes^8,14 and the third was based on coroners’ reports.¹⁰ Although the sons’ personality traits were not described, the fathers were noted to be “domineering and aggressive,” and their relationships with their sons were “cruel and unusual.”⁸ In our review of these studies, >50% of sons were diagnosed with schizophrenia (weighted mean 60%, range 49% to 80%). Many perpetrators exhibited psychotic symptoms, including delusions and hallucinations. In 1 study, 40% of sons with psychotic symptoms perceived their fathers as posing “threats of physical or psychological annihilation.”¹⁴

In 2 of these studies all of the sons were single or separated from their spouses.^8,14 Most killed only their fathers at the time of the act. Immediately before the crime, one-half of the fathers were consuming alcohol and/or arguing with their sons. Ninety percent of the fathers were killed by excessive violence. Following the acts, the sons described feeling “relief rather than remorse or guilt…leading to a feeling of freedom from the abnormal relationship.”¹⁴ One study noted that, in the course of legal proceedings, one-fifth were deemed competent to stand trial and the others were found to be incompetent and hospitalized.¹⁴

Table 1

Sons who kill their parents: Schizophrenia is common

Daughters who commit parricide

d’Orban and O’Connor conducted the only major study examining women who commit parricide,⁹ a retrospective evaluation of 17 women who killed a parent and were housed in a prison or hospital. The authors highlight the importance of delusional beliefs as a motive for parricide (Table 2).⁹

In a 1970 Japanese study of 21 women who killed parents or in-laws, half of the victims were mothers-in-law, but none were biological mothers.¹⁹ According to the authors, this finding suggests that relationships between Japanese women and their mothers-in-law often are particularly contentious; however, no research has examined this theory in the United States.

Matricide by daughters. In the d’Orban and O’Connor study,⁹ >80% of women who committed parricide killed their mothers. In general, the daughters were described as being “in mid-life, living alone with an elderly, domineering mother in marked social isolation.” The parent-child relationship was “characterized by mutual hostility and dependence.” Seventy-five percent of the daughters suffered from psychotic illness. Extreme violence often was used.

Patricide by daughters. Of the 3 women who killed their fathers in d’Orban and O’Connor’s study,⁹ none were psychotic. Furthermore, 2 women had no psychiatric diagnosis—the third had antisocial personality disorder—and “killed tyrannical fathers in response to prolonged parental violence.” One woman reported that she was forced into a long-term incestuous relationship before killing her father. The women who killed their fathers were younger (mean age 21.3) than those who killed their mothers (mean age 39.5).

Table 2

Daughters who kill their parents: Strained relationships

Other perpetrators and victims

Patricide is most often committed by adults²⁰; however, some important conclusions can be drawn regarding juveniles who kill their parents (Table 3).^21-27 The most common scenario is of adolescent boys who have no history of psychosis and kill their fathers in a burst of rage brought on by ongoing abuse from parents. These murders typically are followed by feelings of relief rather than remorse.^21-27

Stepparents often have a more challenging relationship with children than biological parents.²⁸ Research indicates that stepparents are more likely than biological parents to be killed by juvenile offenders.²⁹ Also, stepparent victims tended to be younger than biological parent victims.²⁹

Table 3

Characteristics of juveniles who kill their parents or stepparents

Clinical applications

Ask adult schizophrenia patients living with a parent about the quality of the relationship. If the relationship is characterized by conflict or abuse or if psychotic symptoms are present, assess for violent thoughts toward the parent. For patients with uncontrolled psychosis coupled with a contentious parental relationship, in addition to aggressively treating psychotic symptoms, consider initiating family therapy, anger management classes, group home placement, or involuntary hospitalization to lower the risk of parricide.

Related resources

• Heide KM, Boots DP. A comparative analysis of media reports of U.S. parricide cases with officially reported national crime data and the psychiatric and psychological literature. Int J Offender Ther Comp Criminol. 2007;51(6):646-675.
• Jacobs A. On matricide: myth, psychoanalysis, and the law of the mother. New York, NY: Columbia University Press; 2007.

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/parricide-characteristics-of-sons-and.html#comments

Mr. B, age 37, is single and lives with his elderly mother. Since being diagnosed with schizophrenia in his early 20s, he has been intermittently compliant with antipsychotic therapy. When unmedicated, Mr. B develops paranoid delusions and becomes preoccupied with the idea that his mother is plotting to kill him. He has been hospitalized twice in the last 5 years for physical aggression toward his mother. In the last 10 years, Mr. B has been placed in several group homes, but when he takes his medications, he is able to convince his mother to allow him to live with her.

During his most recent stay in his mother’s home, Mr. B again stops taking his psychotropic medications and decompensates. His mother becomes concerned about her son’s paranoid behavior—such as trying to listen in on her telephone conversations and smelling his food before he eats it—and considers having her son involuntarily committed. One day, after she prepares Mr. B a sandwich, he decides the meat is poisoned. When his mother tries to convince him to eat the sandwich, Mr. B becomes enraged and stabs her 54 times with a kitchen knife.

Mr. B is arrested without resistance. He is adjudicated incompetent to stand trial and is restored to competency within 3 months. Mr. B is found not guilty by reason of insanity (NGRI) and is civilly committed to a state psychiatric facility.

Parricide—killing one’s parents—once was referred to as “the schizophrenic crime,”¹ but is now recognized as being more complex.² In the United States, parricides accounted for 2% of all homicides from 1976 to 1998,³ which is consistent with studies from France⁴ and the United Kingdom.⁵ Parricide’s scandalous nature has long attracted the public’s fascination (see this article at CurrentPsychiatry.com).

This article primarily focuses on the interplay of the diagnostic and demographic factors seen in adults who kill their biological parents but briefly notes differences seen in juvenile perpetrators and those who kill their stepparents. Knowledge of these characteristics can help clinicians identify and more safely manage patients who may be at risk of harming their parents.

Box

A limited evidence base

The common themes found in the literature on parricide should be interpreted cautiously because of the limitations of this research. The number of individuals assessed in these studies often is small, which limits the statistical power of the findings. Studies often are conducted in forensic hospitals, which excludes those who are imprisoned or commit suicide following the acts. Finally, most individuals studied were diagnosed with a psychiatric disorder after the crime, which makes it difficult to distinguish the primary illness from the crime’s effect on a person’s mental state. Additionally, some individuals may be tempted to exaggerate or feign psychiatric symptoms in an effort to be found NGRI or granted leniency during sentencing. Despite these limitations, several conclusions can be drawn from these investigations.

The sex of the victims and perpetrators needs to be carefully considered when reviewing characteristics of those who commit parricide. Killing a mother is matricide, and killing a father is patricide.

Sons who kill their parents

Men are more likely to kill their parents than women.^6-9 In a study of 5,488 cases of parricide in the United States, 4,738 (86%) of perpetrators were male.³ Common characteristics of men who commit parricide are listed in Table 1.^5,8,10-14

Matricide by sons. Although sons kill their fathers more often than their mothers,¹⁵ authors writing about parricide commonly focus on men who commit matricide. Wertham described sons who kill their mothers in terms of the “Orestes Complex,” which refers to ambivalent feelings toward the mother that ultimately manifest in homicidal rage. He noted that many matricides are committed with excessive force, occur in the bedroom, and are precipitated by trivial reasons. Wertham stated that these crimes represent the son’s unconscious hatred for his mother superimposed on sexual desire for her.¹⁶ Sigmund Freud argued that matricide served as a displacement defense against incestuous impulses.¹⁷

In 5 studies that looked at sons who killed their mothers (n=13 to 58),^5,10-13 most of which examined men residing in forensic hospitals after the crime, perpetrators were noted to be immature, dependent, and passive. In a study of 16 men with schizophrenia who committed matricide, subjects perceived themselves as “weak, small, inadequate, hopeless, doubtful about sexual identity, dependent, and unable to accept a separate, adult male role.”¹¹ Mothers generally were domineering, demanding, and possessive.

Based on our literature review, most men who committed matricide had a schizophrenia diagnosis (weighted mean 72%, range 50% to 100%); other diagnoses included depression and personality disorders. Many men were experiencing psychosis shortly before the crime, and their acts were influenced by persecutory delusions and/or auditory hallucinations. Approximately one-quarter of sons killed their mothers for altruistic reasons, such as to relieve actual or perceived suffering.

Nearly all men in these 5 studies were single and lived with their mothers before killing them, and many of the perpetrators’ fathers were absent. Mothers often were the only victims of their sons’ violent acts. In addition to delusional beliefs, sons were motivated to kill their mothers for various reasons, including threatened separation or minor arguments (eg, over food or money). Many of these homicides took place in the home. Sharp or blunt objects were the most common weapons, but guns and strangulation/asphyxiation also were used. Approximately one-half of the men used excessive violence; for example, 1 victim had 177 stab wounds. After the crimes, the perpetrators generally expressed remorse or relief.

Patricide by sons. Psychoanalysts may consider the Oedipal Complex to be the primary impetus for a son to commit patricide. By eliminating his father the son gains possession of his mother.¹⁸ Three studies looked at sons who killed their fathers; 2 examined 10 perpetrators residing in a forensic hospital after the crimes^8,14 and the third was based on coroners’ reports.¹⁰ Although the sons’ personality traits were not described, the fathers were noted to be “domineering and aggressive,” and their relationships with their sons were “cruel and unusual.”⁸ In our review of these studies, >50% of sons were diagnosed with schizophrenia (weighted mean 60%, range 49% to 80%). Many perpetrators exhibited psychotic symptoms, including delusions and hallucinations. In 1 study, 40% of sons with psychotic symptoms perceived their fathers as posing “threats of physical or psychological annihilation.”¹⁴

In 2 of these studies all of the sons were single or separated from their spouses.^8,14 Most killed only their fathers at the time of the act. Immediately before the crime, one-half of the fathers were consuming alcohol and/or arguing with their sons. Ninety percent of the fathers were killed by excessive violence. Following the acts, the sons described feeling “relief rather than remorse or guilt…leading to a feeling of freedom from the abnormal relationship.”¹⁴ One study noted that, in the course of legal proceedings, one-fifth were deemed competent to stand trial and the others were found to be incompetent and hospitalized.¹⁴

Table 1

Sons who kill their parents: Schizophrenia is common

Daughters who commit parricide

d’Orban and O’Connor conducted the only major study examining women who commit parricide,⁹ a retrospective evaluation of 17 women who killed a parent and were housed in a prison or hospital. The authors highlight the importance of delusional beliefs as a motive for parricide (Table 2).⁹

In a 1970 Japanese study of 21 women who killed parents or in-laws, half of the victims were mothers-in-law, but none were biological mothers.¹⁹ According to the authors, this finding suggests that relationships between Japanese women and their mothers-in-law often are particularly contentious; however, no research has examined this theory in the United States.

Matricide by daughters. In the d’Orban and O’Connor study,⁹ >80% of women who committed parricide killed their mothers. In general, the daughters were described as being “in mid-life, living alone with an elderly, domineering mother in marked social isolation.” The parent-child relationship was “characterized by mutual hostility and dependence.” Seventy-five percent of the daughters suffered from psychotic illness. Extreme violence often was used.

Patricide by daughters. Of the 3 women who killed their fathers in d’Orban and O’Connor’s study,⁹ none were psychotic. Furthermore, 2 women had no psychiatric diagnosis—the third had antisocial personality disorder—and “killed tyrannical fathers in response to prolonged parental violence.” One woman reported that she was forced into a long-term incestuous relationship before killing her father. The women who killed their fathers were younger (mean age 21.3) than those who killed their mothers (mean age 39.5).

Table 2

Daughters who kill their parents: Strained relationships

Other perpetrators and victims

Patricide is most often committed by adults²⁰; however, some important conclusions can be drawn regarding juveniles who kill their parents (Table 3).^21-27 The most common scenario is of adolescent boys who have no history of psychosis and kill their fathers in a burst of rage brought on by ongoing abuse from parents. These murders typically are followed by feelings of relief rather than remorse.^21-27

Stepparents often have a more challenging relationship with children than biological parents.²⁸ Research indicates that stepparents are more likely than biological parents to be killed by juvenile offenders.²⁹ Also, stepparent victims tended to be younger than biological parent victims.²⁹

Table 3

Characteristics of juveniles who kill their parents or stepparents

Clinical applications

Ask adult schizophrenia patients living with a parent about the quality of the relationship. If the relationship is characterized by conflict or abuse or if psychotic symptoms are present, assess for violent thoughts toward the parent. For patients with uncontrolled psychosis coupled with a contentious parental relationship, in addition to aggressively treating psychotic symptoms, consider initiating family therapy, anger management classes, group home placement, or involuntary hospitalization to lower the risk of parricide.

Related resources

• Heide KM, Boots DP. A comparative analysis of media reports of U.S. parricide cases with officially reported national crime data and the psychiatric and psychological literature. Int J Offender Ther Comp Criminol. 2007;51(6):646-675.
• Jacobs A. On matricide: myth, psychoanalysis, and the law of the mother. New York, NY: Columbia University Press; 2007.

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Discuss this article at http://currentpsychiatry.blogspot.com/2010/11/parricide-characteristics-of-sons-and.html#comments

Mr. B, age 37, is single and lives with his elderly mother. Since being diagnosed with schizophrenia in his early 20s, he has been intermittently compliant with antipsychotic therapy. When unmedicated, Mr. B develops paranoid delusions and becomes preoccupied with the idea that his mother is plotting to kill him. He has been hospitalized twice in the last 5 years for physical aggression toward his mother. In the last 10 years, Mr. B has been placed in several group homes, but when he takes his medications, he is able to convince his mother to allow him to live with her.

During his most recent stay in his mother’s home, Mr. B again stops taking his psychotropic medications and decompensates. His mother becomes concerned about her son’s paranoid behavior—such as trying to listen in on her telephone conversations and smelling his food before he eats it—and considers having her son involuntarily committed. One day, after she prepares Mr. B a sandwich, he decides the meat is poisoned. When his mother tries to convince him to eat the sandwich, Mr. B becomes enraged and stabs her 54 times with a kitchen knife.

Mr. B is arrested without resistance. He is adjudicated incompetent to stand trial and is restored to competency within 3 months. Mr. B is found not guilty by reason of insanity (NGRI) and is civilly committed to a state psychiatric facility.

Parricide—killing one’s parents—once was referred to as “the schizophrenic crime,”¹ but is now recognized as being more complex.² In the United States, parricides accounted for 2% of all homicides from 1976 to 1998,³ which is consistent with studies from France⁴ and the United Kingdom.⁵ Parricide’s scandalous nature has long attracted the public’s fascination (see this article at CurrentPsychiatry.com).

This article primarily focuses on the interplay of the diagnostic and demographic factors seen in adults who kill their biological parents but briefly notes differences seen in juvenile perpetrators and those who kill their stepparents. Knowledge of these characteristics can help clinicians identify and more safely manage patients who may be at risk of harming their parents.

Box

A limited evidence base

The common themes found in the literature on parricide should be interpreted cautiously because of the limitations of this research. The number of individuals assessed in these studies often is small, which limits the statistical power of the findings. Studies often are conducted in forensic hospitals, which excludes those who are imprisoned or commit suicide following the acts. Finally, most individuals studied were diagnosed with a psychiatric disorder after the crime, which makes it difficult to distinguish the primary illness from the crime’s effect on a person’s mental state. Additionally, some individuals may be tempted to exaggerate or feign psychiatric symptoms in an effort to be found NGRI or granted leniency during sentencing. Despite these limitations, several conclusions can be drawn from these investigations.

The sex of the victims and perpetrators needs to be carefully considered when reviewing characteristics of those who commit parricide. Killing a mother is matricide, and killing a father is patricide.

Sons who kill their parents

Men are more likely to kill their parents than women.^6-9 In a study of 5,488 cases of parricide in the United States, 4,738 (86%) of perpetrators were male.³ Common characteristics of men who commit parricide are listed in Table 1.^5,8,10-14

Matricide by sons. Although sons kill their fathers more often than their mothers,¹⁵ authors writing about parricide commonly focus on men who commit matricide. Wertham described sons who kill their mothers in terms of the “Orestes Complex,” which refers to ambivalent feelings toward the mother that ultimately manifest in homicidal rage. He noted that many matricides are committed with excessive force, occur in the bedroom, and are precipitated by trivial reasons. Wertham stated that these crimes represent the son’s unconscious hatred for his mother superimposed on sexual desire for her.¹⁶ Sigmund Freud argued that matricide served as a displacement defense against incestuous impulses.¹⁷

In 5 studies that looked at sons who killed their mothers (n=13 to 58),^5,10-13 most of which examined men residing in forensic hospitals after the crime, perpetrators were noted to be immature, dependent, and passive. In a study of 16 men with schizophrenia who committed matricide, subjects perceived themselves as “weak, small, inadequate, hopeless, doubtful about sexual identity, dependent, and unable to accept a separate, adult male role.”¹¹ Mothers generally were domineering, demanding, and possessive.

Based on our literature review, most men who committed matricide had a schizophrenia diagnosis (weighted mean 72%, range 50% to 100%); other diagnoses included depression and personality disorders. Many men were experiencing psychosis shortly before the crime, and their acts were influenced by persecutory delusions and/or auditory hallucinations. Approximately one-quarter of sons killed their mothers for altruistic reasons, such as to relieve actual or perceived suffering.

Nearly all men in these 5 studies were single and lived with their mothers before killing them, and many of the perpetrators’ fathers were absent. Mothers often were the only victims of their sons’ violent acts. In addition to delusional beliefs, sons were motivated to kill their mothers for various reasons, including threatened separation or minor arguments (eg, over food or money). Many of these homicides took place in the home. Sharp or blunt objects were the most common weapons, but guns and strangulation/asphyxiation also were used. Approximately one-half of the men used excessive violence; for example, 1 victim had 177 stab wounds. After the crimes, the perpetrators generally expressed remorse or relief.

Patricide by sons. Psychoanalysts may consider the Oedipal Complex to be the primary impetus for a son to commit patricide. By eliminating his father the son gains possession of his mother.¹⁸ Three studies looked at sons who killed their fathers; 2 examined 10 perpetrators residing in a forensic hospital after the crimes^8,14 and the third was based on coroners’ reports.¹⁰ Although the sons’ personality traits were not described, the fathers were noted to be “domineering and aggressive,” and their relationships with their sons were “cruel and unusual.”⁸ In our review of these studies, >50% of sons were diagnosed with schizophrenia (weighted mean 60%, range 49% to 80%). Many perpetrators exhibited psychotic symptoms, including delusions and hallucinations. In 1 study, 40% of sons with psychotic symptoms perceived their fathers as posing “threats of physical or psychological annihilation.”¹⁴

In 2 of these studies all of the sons were single or separated from their spouses.^8,14 Most killed only their fathers at the time of the act. Immediately before the crime, one-half of the fathers were consuming alcohol and/or arguing with their sons. Ninety percent of the fathers were killed by excessive violence. Following the acts, the sons described feeling “relief rather than remorse or guilt…leading to a feeling of freedom from the abnormal relationship.”¹⁴ One study noted that, in the course of legal proceedings, one-fifth were deemed competent to stand trial and the others were found to be incompetent and hospitalized.¹⁴

Table 1

Sons who kill their parents: Schizophrenia is common

Daughters who commit parricide

d’Orban and O’Connor conducted the only major study examining women who commit parricide,⁹ a retrospective evaluation of 17 women who killed a parent and were housed in a prison or hospital. The authors highlight the importance of delusional beliefs as a motive for parricide (Table 2).⁹

In a 1970 Japanese study of 21 women who killed parents or in-laws, half of the victims were mothers-in-law, but none were biological mothers.¹⁹ According to the authors, this finding suggests that relationships between Japanese women and their mothers-in-law often are particularly contentious; however, no research has examined this theory in the United States.

Matricide by daughters. In the d’Orban and O’Connor study,⁹ >80% of women who committed parricide killed their mothers. In general, the daughters were described as being “in mid-life, living alone with an elderly, domineering mother in marked social isolation.” The parent-child relationship was “characterized by mutual hostility and dependence.” Seventy-five percent of the daughters suffered from psychotic illness. Extreme violence often was used.

Patricide by daughters. Of the 3 women who killed their fathers in d’Orban and O’Connor’s study,⁹ none were psychotic. Furthermore, 2 women had no psychiatric diagnosis—the third had antisocial personality disorder—and “killed tyrannical fathers in response to prolonged parental violence.” One woman reported that she was forced into a long-term incestuous relationship before killing her father. The women who killed their fathers were younger (mean age 21.3) than those who killed their mothers (mean age 39.5).

Table 2

Daughters who kill their parents: Strained relationships

Other perpetrators and victims

Patricide is most often committed by adults²⁰; however, some important conclusions can be drawn regarding juveniles who kill their parents (Table 3).^21-27 The most common scenario is of adolescent boys who have no history of psychosis and kill their fathers in a burst of rage brought on by ongoing abuse from parents. These murders typically are followed by feelings of relief rather than remorse.^21-27

Stepparents often have a more challenging relationship with children than biological parents.²⁸ Research indicates that stepparents are more likely than biological parents to be killed by juvenile offenders.²⁹ Also, stepparent victims tended to be younger than biological parent victims.²⁹

Table 3

Characteristics of juveniles who kill their parents or stepparents

Clinical applications

Ask adult schizophrenia patients living with a parent about the quality of the relationship. If the relationship is characterized by conflict or abuse or if psychotic symptoms are present, assess for violent thoughts toward the parent. For patients with uncontrolled psychosis coupled with a contentious parental relationship, in addition to aggressively treating psychotic symptoms, consider initiating family therapy, anger management classes, group home placement, or involuntary hospitalization to lower the risk of parricide.

Related resources

• Heide KM, Boots DP. A comparative analysis of media reports of U.S. parricide cases with officially reported national crime data and the psychiatric and psychological literature. Int J Offender Ther Comp Criminol. 2007;51(6):646-675.
• Jacobs A. On matricide: myth, psychoanalysis, and the law of the mother. New York, NY: Columbia University Press; 2007.

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

CASE: Food issues

Ms. A, age 62, has a 40-year history of paranoid schizophrenia, which has been well controlled with olanzapine, 20 mg/d, for many years. Two weeks ago, she stops taking her medication and is brought to a state-run psychiatric hospital by law enforcement officers because of worsening paranoia and hostility. She is disheveled, intermittently denudative, and confused. Ms. A has type II diabetes, gastroesophageal reflux disease, obesity (body mass index of 34.75 kg/m²), and poor dentition. She has no history of substance abuse.

During the first 2 days in the hospital Ms. A refuses to eat, stating that the food is “poisoned,” but accepts 1 oral dose of aripiprazole, 25 mg. On hospital day 3, Ms. A is less hostile and eats dinner with the other patients. A few minutes after beginning her meal, Ms. A abruptly stands up and puts her hands to her throat. She looks frightened, and cannot speak.

A staff member asks Ms. A if she is choking and she nods. Because the psychiatric hospital does not have an emergency room, the staff call 911, and a staff member gives Ms. A back blows, but no food is forced out. Next, nursing staff start abdominal thrusts (Heimlich maneuver) without success. Ms. A then loses consciousness and the staff lowers her to the ground. The nurse looks in Ms. A’s mouth, but can’t see what is blocking her throat. Attempts to provide rescue breathing are unproductive because a foreign body obstructs Ms. A’s airway. A staff member continues abdominal thrusts once Ms. A is on the ground. She has no pulse, and CPR is initiated.

Emergency medical technicians arrive within 7 minutes and suction a piece of hot dog from Ms. A’s trachea. She is then taken to a nearby emergency department, where neurologic examination reveals signs of brain death.

Ms. A dies a few days later. The cause of death is respiratory and cardiac failure secondary to choking and foreign body obstruction. A review of Ms. A’s history reveals she had past episodes of choking and a habit of rapidly ingesting large amounts of food (tachyphagia).

The authors’ observations

The term “café coronary” describes sudden unexpected death caused by airway obstruction by food.¹ In 1975, Henry Heimlich described the abdominal thrusting maneuver recommended to prevent these fatalities.² For more than a century, choking has been recognized as a cause of death in individuals with severe mental illness.³ An analysis of sudden deaths among psychiatric in-patients in Ireland found that choking accounted for 10% of deaths over 10 years.⁴ An Australian study reported that individuals with schizophrenia had 20-fold greater risk of death by choking than the general population.⁵ Another study found the mortality rate attributable to choking was 8-fold higher for psychiatric inpatients than the general population,⁶ and a study in the United States reported that for every 1,000 deaths among psychiatric inpatients, 0.6 were caused by asphyxia,⁷ which is 100 times greater than the general population reported in the same time.⁸

Physiological mechanisms associated with impaired swallowing include:

• dopamine blockade, which could produce central and peripheral impairment of swallowing⁹
• anticholinergic effect leading to impaired esophageal motility
• impaired gag reflex.¹⁰

Multiple factors increase mentally ill individuals’ risk of death by choking (Table 1).¹¹ Patients with schizophrenia may exhibit impaired swallowing mechanism, irrespective of psychotropic medications.¹² Schizophrenia patients also could exhibit pica behavior—persistent and culturally and developmentally inappropriate ingestion of non-nutritive substances. Examples of pica behavior include ingesting rolled can lids¹³ and coins^14,15 and coprophagia.¹⁶ Pica behavior increases the risk for choking, and has been implicated in deaths of individuals with schizophrenia.¹⁷

Medications with dopamine blocking and anticholinergic effects may increase choking risk.¹⁸ These medications could produce extrapyramidal side effects and parkinsonism, which might impair swallowing. Psychotropic medications could increase appetite and food craving, which in turn may lead to overeating and tachyphagia. In addition, many individuals suffering from severe mental illness have poor dentition, which could make chewing food difficult.¹⁹ Psychiatric patients are more likely to be obese, which also increases the risk of choking.

Table 1

Risk factors for choking in mentally ill patients

OUTCOME: Prevention strategies

New Hampshire Hospital’s administration implemented a plan to increase the staff’s awareness of choking risks in mentally ill patients. Nurses complete nutrition screens along with the initial nursing database assessment on all patients during the admission process, and are encouraged to contact registered dieticians for a nutrition review and assessment if a psychiatric patient is thought to be at risk for choking. Registered dieticians work with nursing staff to promptly complete nutrition assessments and address eating-related problems.

Direct care staff were reminded that all inpatient units have a battery-powered, portable compact suction unit available that can be used in a choking emergency. The hospital’s cardiopulmonary resuscitation instructors emphasize the importance of the abdominal thrust maneuver during all staff training sessions.

The hospital’s administration and staff did not reach a consensus on whether physicians should attempt a tracheotomy when other measures to dislodge a foreign object from a patient’s throat fail. Instead, the focus remains on assessing and treating the clinical emergency and obtaining rapid intervention by emergency medical technicians.

The authors’ observations

The following recommendations may help minimize or prevent choking events in inpatient units:

• Ensure all staff who care for patients are trained regularly on emergency first aid for choking victims, including proper use of abdominal thrusts (Heimlich maneuver) (Table 2).²⁰
• Educate staff about which patients may be at higher risk for choking.
• Assess for a history of choking incidents and/or the presence of swallowing problems in patients at risk for choking.
• Supervise meals and instruct staff to look for patients who display dysphagia.
• Consider ordering a swallowing evaluation performed by a speech therapist in patients who manifest dysphagia.
• Avoid polypharmacy of drugs with anticholinergic and/or potent dopamine blocking effects, such as olanzapine, risperidone, or haloperidol.
• Teach safe eating habits to patients who are at risk for choking.
• Contact outpatient care providers of patients at risk for choking and inform them of the need for further education on safe eating habits, a dietary evaluation, and/or a swallowing evaluation.

Implementing these measures may reduce choking incidents and could save lives.

Table 2

American Red Cross guidelines for treating a conscious, choking adult

Related Resources

• Hwang SJ, Tsai SJ, Chen IJ, et al. Choking incidents among psychiatric inpatients: a retrospective study in Chutung Veterans General Hospital. J Chin Med Assoc. 2010;73(8):419-424.
• American College of Emergency Physicians Foundation. What to do in a medical emergency. Choking. www.emergencycareforyou.org/EmergencyManual/WhatToDoInMedicalEmergency/Default.aspx?id=224.

Drug Brand Names

• Aripiprazole • Abilify
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Risperidone • Risperdal

Disclosures

Dr. de Nesnera reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Folks is a consultant and speaker for Pfizer Inc., a speaker for Forest Pharmaceuticals, and has received a research grant from Janssen Pharmaceuticals.

CASE: Food issues

Ms. A, age 62, has a 40-year history of paranoid schizophrenia, which has been well controlled with olanzapine, 20 mg/d, for many years. Two weeks ago, she stops taking her medication and is brought to a state-run psychiatric hospital by law enforcement officers because of worsening paranoia and hostility. She is disheveled, intermittently denudative, and confused. Ms. A has type II diabetes, gastroesophageal reflux disease, obesity (body mass index of 34.75 kg/m²), and poor dentition. She has no history of substance abuse.

During the first 2 days in the hospital Ms. A refuses to eat, stating that the food is “poisoned,” but accepts 1 oral dose of aripiprazole, 25 mg. On hospital day 3, Ms. A is less hostile and eats dinner with the other patients. A few minutes after beginning her meal, Ms. A abruptly stands up and puts her hands to her throat. She looks frightened, and cannot speak.

A staff member asks Ms. A if she is choking and she nods. Because the psychiatric hospital does not have an emergency room, the staff call 911, and a staff member gives Ms. A back blows, but no food is forced out. Next, nursing staff start abdominal thrusts (Heimlich maneuver) without success. Ms. A then loses consciousness and the staff lowers her to the ground. The nurse looks in Ms. A’s mouth, but can’t see what is blocking her throat. Attempts to provide rescue breathing are unproductive because a foreign body obstructs Ms. A’s airway. A staff member continues abdominal thrusts once Ms. A is on the ground. She has no pulse, and CPR is initiated.

Emergency medical technicians arrive within 7 minutes and suction a piece of hot dog from Ms. A’s trachea. She is then taken to a nearby emergency department, where neurologic examination reveals signs of brain death.

Ms. A dies a few days later. The cause of death is respiratory and cardiac failure secondary to choking and foreign body obstruction. A review of Ms. A’s history reveals she had past episodes of choking and a habit of rapidly ingesting large amounts of food (tachyphagia).

The authors’ observations

The term “café coronary” describes sudden unexpected death caused by airway obstruction by food.¹ In 1975, Henry Heimlich described the abdominal thrusting maneuver recommended to prevent these fatalities.² For more than a century, choking has been recognized as a cause of death in individuals with severe mental illness.³ An analysis of sudden deaths among psychiatric in-patients in Ireland found that choking accounted for 10% of deaths over 10 years.⁴ An Australian study reported that individuals with schizophrenia had 20-fold greater risk of death by choking than the general population.⁵ Another study found the mortality rate attributable to choking was 8-fold higher for psychiatric inpatients than the general population,⁶ and a study in the United States reported that for every 1,000 deaths among psychiatric inpatients, 0.6 were caused by asphyxia,⁷ which is 100 times greater than the general population reported in the same time.⁸

Physiological mechanisms associated with impaired swallowing include:

• dopamine blockade, which could produce central and peripheral impairment of swallowing⁹
• anticholinergic effect leading to impaired esophageal motility
• impaired gag reflex.¹⁰

Multiple factors increase mentally ill individuals’ risk of death by choking (Table 1).¹¹ Patients with schizophrenia may exhibit impaired swallowing mechanism, irrespective of psychotropic medications.¹² Schizophrenia patients also could exhibit pica behavior—persistent and culturally and developmentally inappropriate ingestion of non-nutritive substances. Examples of pica behavior include ingesting rolled can lids¹³ and coins^14,15 and coprophagia.¹⁶ Pica behavior increases the risk for choking, and has been implicated in deaths of individuals with schizophrenia.¹⁷

Medications with dopamine blocking and anticholinergic effects may increase choking risk.¹⁸ These medications could produce extrapyramidal side effects and parkinsonism, which might impair swallowing. Psychotropic medications could increase appetite and food craving, which in turn may lead to overeating and tachyphagia. In addition, many individuals suffering from severe mental illness have poor dentition, which could make chewing food difficult.¹⁹ Psychiatric patients are more likely to be obese, which also increases the risk of choking.

Table 1

Risk factors for choking in mentally ill patients

OUTCOME: Prevention strategies

New Hampshire Hospital’s administration implemented a plan to increase the staff’s awareness of choking risks in mentally ill patients. Nurses complete nutrition screens along with the initial nursing database assessment on all patients during the admission process, and are encouraged to contact registered dieticians for a nutrition review and assessment if a psychiatric patient is thought to be at risk for choking. Registered dieticians work with nursing staff to promptly complete nutrition assessments and address eating-related problems.

Direct care staff were reminded that all inpatient units have a battery-powered, portable compact suction unit available that can be used in a choking emergency. The hospital’s cardiopulmonary resuscitation instructors emphasize the importance of the abdominal thrust maneuver during all staff training sessions.

The hospital’s administration and staff did not reach a consensus on whether physicians should attempt a tracheotomy when other measures to dislodge a foreign object from a patient’s throat fail. Instead, the focus remains on assessing and treating the clinical emergency and obtaining rapid intervention by emergency medical technicians.

The authors’ observations

The following recommendations may help minimize or prevent choking events in inpatient units:

• Ensure all staff who care for patients are trained regularly on emergency first aid for choking victims, including proper use of abdominal thrusts (Heimlich maneuver) (Table 2).²⁰
• Educate staff about which patients may be at higher risk for choking.
• Assess for a history of choking incidents and/or the presence of swallowing problems in patients at risk for choking.
• Supervise meals and instruct staff to look for patients who display dysphagia.
• Consider ordering a swallowing evaluation performed by a speech therapist in patients who manifest dysphagia.
• Avoid polypharmacy of drugs with anticholinergic and/or potent dopamine blocking effects, such as olanzapine, risperidone, or haloperidol.
• Teach safe eating habits to patients who are at risk for choking.
• Contact outpatient care providers of patients at risk for choking and inform them of the need for further education on safe eating habits, a dietary evaluation, and/or a swallowing evaluation.

Implementing these measures may reduce choking incidents and could save lives.

Table 2

American Red Cross guidelines for treating a conscious, choking adult

Related Resources

• Hwang SJ, Tsai SJ, Chen IJ, et al. Choking incidents among psychiatric inpatients: a retrospective study in Chutung Veterans General Hospital. J Chin Med Assoc. 2010;73(8):419-424.
• American College of Emergency Physicians Foundation. What to do in a medical emergency. Choking. www.emergencycareforyou.org/EmergencyManual/WhatToDoInMedicalEmergency/Default.aspx?id=224.

Drug Brand Names

• Aripiprazole • Abilify
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Risperidone • Risperdal

Disclosures

Dr. de Nesnera reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Folks is a consultant and speaker for Pfizer Inc., a speaker for Forest Pharmaceuticals, and has received a research grant from Janssen Pharmaceuticals.

CASE: Food issues

Ms. A, age 62, has a 40-year history of paranoid schizophrenia, which has been well controlled with olanzapine, 20 mg/d, for many years. Two weeks ago, she stops taking her medication and is brought to a state-run psychiatric hospital by law enforcement officers because of worsening paranoia and hostility. She is disheveled, intermittently denudative, and confused. Ms. A has type II diabetes, gastroesophageal reflux disease, obesity (body mass index of 34.75 kg/m²), and poor dentition. She has no history of substance abuse.

During the first 2 days in the hospital Ms. A refuses to eat, stating that the food is “poisoned,” but accepts 1 oral dose of aripiprazole, 25 mg. On hospital day 3, Ms. A is less hostile and eats dinner with the other patients. A few minutes after beginning her meal, Ms. A abruptly stands up and puts her hands to her throat. She looks frightened, and cannot speak.

A staff member asks Ms. A if she is choking and she nods. Because the psychiatric hospital does not have an emergency room, the staff call 911, and a staff member gives Ms. A back blows, but no food is forced out. Next, nursing staff start abdominal thrusts (Heimlich maneuver) without success. Ms. A then loses consciousness and the staff lowers her to the ground. The nurse looks in Ms. A’s mouth, but can’t see what is blocking her throat. Attempts to provide rescue breathing are unproductive because a foreign body obstructs Ms. A’s airway. A staff member continues abdominal thrusts once Ms. A is on the ground. She has no pulse, and CPR is initiated.

Emergency medical technicians arrive within 7 minutes and suction a piece of hot dog from Ms. A’s trachea. She is then taken to a nearby emergency department, where neurologic examination reveals signs of brain death.

Ms. A dies a few days later. The cause of death is respiratory and cardiac failure secondary to choking and foreign body obstruction. A review of Ms. A’s history reveals she had past episodes of choking and a habit of rapidly ingesting large amounts of food (tachyphagia).

The authors’ observations

The term “café coronary” describes sudden unexpected death caused by airway obstruction by food.¹ In 1975, Henry Heimlich described the abdominal thrusting maneuver recommended to prevent these fatalities.² For more than a century, choking has been recognized as a cause of death in individuals with severe mental illness.³ An analysis of sudden deaths among psychiatric in-patients in Ireland found that choking accounted for 10% of deaths over 10 years.⁴ An Australian study reported that individuals with schizophrenia had 20-fold greater risk of death by choking than the general population.⁵ Another study found the mortality rate attributable to choking was 8-fold higher for psychiatric inpatients than the general population,⁶ and a study in the United States reported that for every 1,000 deaths among psychiatric inpatients, 0.6 were caused by asphyxia,⁷ which is 100 times greater than the general population reported in the same time.⁸

Physiological mechanisms associated with impaired swallowing include:

• dopamine blockade, which could produce central and peripheral impairment of swallowing⁹
• anticholinergic effect leading to impaired esophageal motility
• impaired gag reflex.¹⁰

Multiple factors increase mentally ill individuals’ risk of death by choking (Table 1).¹¹ Patients with schizophrenia may exhibit impaired swallowing mechanism, irrespective of psychotropic medications.¹² Schizophrenia patients also could exhibit pica behavior—persistent and culturally and developmentally inappropriate ingestion of non-nutritive substances. Examples of pica behavior include ingesting rolled can lids¹³ and coins^14,15 and coprophagia.¹⁶ Pica behavior increases the risk for choking, and has been implicated in deaths of individuals with schizophrenia.¹⁷

Medications with dopamine blocking and anticholinergic effects may increase choking risk.¹⁸ These medications could produce extrapyramidal side effects and parkinsonism, which might impair swallowing. Psychotropic medications could increase appetite and food craving, which in turn may lead to overeating and tachyphagia. In addition, many individuals suffering from severe mental illness have poor dentition, which could make chewing food difficult.¹⁹ Psychiatric patients are more likely to be obese, which also increases the risk of choking.

Table 1

Risk factors for choking in mentally ill patients

OUTCOME: Prevention strategies

New Hampshire Hospital’s administration implemented a plan to increase the staff’s awareness of choking risks in mentally ill patients. Nurses complete nutrition screens along with the initial nursing database assessment on all patients during the admission process, and are encouraged to contact registered dieticians for a nutrition review and assessment if a psychiatric patient is thought to be at risk for choking. Registered dieticians work with nursing staff to promptly complete nutrition assessments and address eating-related problems.

Direct care staff were reminded that all inpatient units have a battery-powered, portable compact suction unit available that can be used in a choking emergency. The hospital’s cardiopulmonary resuscitation instructors emphasize the importance of the abdominal thrust maneuver during all staff training sessions.

The hospital’s administration and staff did not reach a consensus on whether physicians should attempt a tracheotomy when other measures to dislodge a foreign object from a patient’s throat fail. Instead, the focus remains on assessing and treating the clinical emergency and obtaining rapid intervention by emergency medical technicians.

The authors’ observations

The following recommendations may help minimize or prevent choking events in inpatient units:

• Ensure all staff who care for patients are trained regularly on emergency first aid for choking victims, including proper use of abdominal thrusts (Heimlich maneuver) (Table 2).²⁰
• Educate staff about which patients may be at higher risk for choking.
• Assess for a history of choking incidents and/or the presence of swallowing problems in patients at risk for choking.
• Supervise meals and instruct staff to look for patients who display dysphagia.
• Consider ordering a swallowing evaluation performed by a speech therapist in patients who manifest dysphagia.
• Avoid polypharmacy of drugs with anticholinergic and/or potent dopamine blocking effects, such as olanzapine, risperidone, or haloperidol.
• Teach safe eating habits to patients who are at risk for choking.
• Contact outpatient care providers of patients at risk for choking and inform them of the need for further education on safe eating habits, a dietary evaluation, and/or a swallowing evaluation.

Implementing these measures may reduce choking incidents and could save lives.

Table 2

American Red Cross guidelines for treating a conscious, choking adult

Related Resources

• Hwang SJ, Tsai SJ, Chen IJ, et al. Choking incidents among psychiatric inpatients: a retrospective study in Chutung Veterans General Hospital. J Chin Med Assoc. 2010;73(8):419-424.
• American College of Emergency Physicians Foundation. What to do in a medical emergency. Choking. www.emergencycareforyou.org/EmergencyManual/WhatToDoInMedicalEmergency/Default.aspx?id=224.

Drug Brand Names

• Aripiprazole • Abilify
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Risperidone • Risperdal

Disclosures

Dr. de Nesnera reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Folks is a consultant and speaker for Pfizer Inc., a speaker for Forest Pharmaceuticals, and has received a research grant from Janssen Pharmaceuticals.

Dr. Henry A. Nasrallah’s “Treat the patient, not the disease,” (From the Editor, Current Psychiatry, August 2010, p. 13-14) has given me more joy and hope than you can realize. I thought I was alone. I am chair of psychiatry at an academic inner city community teaching hospital, running a dual diagnosis unit as well. I preface each new student rotation by saying, “Medicine is an art as well as a science. You will learn here how to help patients. Do not answer test questions based on my use of psychotropics.” Of course, as we move along I offer both sides (or more) to all treatment possibilities, but I use more than the average number of off-label treatments.

I am passing on your words to the students, staff, medical executive committee, therapeutic committee, and anyone who will listen.

William J. Annitto, MD, MPH
Chairman, department of psychiatry
Medical director behavioral health
Saint Barnabas Health Care Systems
Newark Beth Israel Medical Center
Newark, NJ

Dr. Henry A. Nasrallah’s “Treat the patient, not the disease,” (From the Editor, Current Psychiatry, August 2010, p. 13-14) has given me more joy and hope than you can realize. I thought I was alone. I am chair of psychiatry at an academic inner city community teaching hospital, running a dual diagnosis unit as well. I preface each new student rotation by saying, “Medicine is an art as well as a science. You will learn here how to help patients. Do not answer test questions based on my use of psychotropics.” Of course, as we move along I offer both sides (or more) to all treatment possibilities, but I use more than the average number of off-label treatments.

I am passing on your words to the students, staff, medical executive committee, therapeutic committee, and anyone who will listen.

William J. Annitto, MD, MPH
Chairman, department of psychiatry
Medical director behavioral health
Saint Barnabas Health Care Systems
Newark Beth Israel Medical Center
Newark, NJ

Dr. Henry A. Nasrallah’s “Treat the patient, not the disease,” (From the Editor, Current Psychiatry, August 2010, p. 13-14) has given me more joy and hope than you can realize. I thought I was alone. I am chair of psychiatry at an academic inner city community teaching hospital, running a dual diagnosis unit as well. I preface each new student rotation by saying, “Medicine is an art as well as a science. You will learn here how to help patients. Do not answer test questions based on my use of psychotropics.” Of course, as we move along I offer both sides (or more) to all treatment possibilities, but I use more than the average number of off-label treatments.

I am passing on your words to the students, staff, medical executive committee, therapeutic committee, and anyone who will listen.

William J. Annitto, MD, MPH
Chairman, department of psychiatry
Medical director behavioral health
Saint Barnabas Health Care Systems
Newark Beth Israel Medical Center
Newark, NJ

Insurance companies and surgical teams usually require patients to undergo a psychiatric evaluation before major surgeries such as organ transplants,¹ amputations, or bariatric procedures because these surgeries are expensive, require patients to change their lifestyle, and use limited resources. Psychiatrists perform pre-surgical evaluations by diagnostic interview, observation, and obtaining collateral information. Your evaluation should address key elements and give the surgical team input about a patient’s suitability for surgery. You also can comment on treatments that would make the patient a better candidate for surgery and plan for post-surgery psychiatric morbidities.

Key elements

Major mental illness. Without adequate treatment, major mood disorders can make a patient unable to undergo surgery. In addition, these types of surgeries are substantial life events that can trigger mood episodes. Educate patients about early signs of relapse and suggest a plan of action for treatment. A patient with an uncontrolled psychotic disorder and poor social support and/or case management is not a good candidate for surgery.

Substance use. Patients with active substance dependence are poor candidates for major surgeries unless they receive substance abuse treatment. During evaluation, motivational interviewing can help guide a patient toward treatment. Ensure that patients whose substance dependence is in remission have adequate support and treatment plans to prevent relapse.

Capacity to make decisions is based on the nature of the procedure and the patient’s ability to understand the process and risk vs benefits. The threshold for capacity can vary based on the procedure and the risks.²

Treatment adherence requires compliance with close medical follow-up, complicated medications, or lifestyle changes. A history of compliance with medical directives, medications, and appointments is important. Collateral information from the surgical team or caregivers can be helpful.

Coping style and strategies. Quiz the patient about internal and external resources they have used to cope with stress. A pattern of decompensation to using primitive defense mechanisms to handle stress suggests that the patient may have a personality disorder and might be a poor surgical candidate. Ability to use relatively mature defense strategies in stressful times suggests a good candidate.

Safety. Active suicidal or homicidal ideation is problematic in patients seeking major surgical interventions. Ensure that the stress of the surgery will not trigger dangerous behaviors. A history of frequent self-harm or impulsive suicidality suggests the that patient may have an unstable axis I or II disorder and might be a poor candidate for major surgery without further treatment.

Insurance companies and surgical teams usually require patients to undergo a psychiatric evaluation before major surgeries such as organ transplants,¹ amputations, or bariatric procedures because these surgeries are expensive, require patients to change their lifestyle, and use limited resources. Psychiatrists perform pre-surgical evaluations by diagnostic interview, observation, and obtaining collateral information. Your evaluation should address key elements and give the surgical team input about a patient’s suitability for surgery. You also can comment on treatments that would make the patient a better candidate for surgery and plan for post-surgery psychiatric morbidities.

Key elements

Major mental illness. Without adequate treatment, major mood disorders can make a patient unable to undergo surgery. In addition, these types of surgeries are substantial life events that can trigger mood episodes. Educate patients about early signs of relapse and suggest a plan of action for treatment. A patient with an uncontrolled psychotic disorder and poor social support and/or case management is not a good candidate for surgery.

Substance use. Patients with active substance dependence are poor candidates for major surgeries unless they receive substance abuse treatment. During evaluation, motivational interviewing can help guide a patient toward treatment. Ensure that patients whose substance dependence is in remission have adequate support and treatment plans to prevent relapse.

Capacity to make decisions is based on the nature of the procedure and the patient’s ability to understand the process and risk vs benefits. The threshold for capacity can vary based on the procedure and the risks.²

Treatment adherence requires compliance with close medical follow-up, complicated medications, or lifestyle changes. A history of compliance with medical directives, medications, and appointments is important. Collateral information from the surgical team or caregivers can be helpful.

Coping style and strategies. Quiz the patient about internal and external resources they have used to cope with stress. A pattern of decompensation to using primitive defense mechanisms to handle stress suggests that the patient may have a personality disorder and might be a poor surgical candidate. Ability to use relatively mature defense strategies in stressful times suggests a good candidate.

Safety. Active suicidal or homicidal ideation is problematic in patients seeking major surgical interventions. Ensure that the stress of the surgery will not trigger dangerous behaviors. A history of frequent self-harm or impulsive suicidality suggests the that patient may have an unstable axis I or II disorder and might be a poor candidate for major surgery without further treatment.

Insurance companies and surgical teams usually require patients to undergo a psychiatric evaluation before major surgeries such as organ transplants,¹ amputations, or bariatric procedures because these surgeries are expensive, require patients to change their lifestyle, and use limited resources. Psychiatrists perform pre-surgical evaluations by diagnostic interview, observation, and obtaining collateral information. Your evaluation should address key elements and give the surgical team input about a patient’s suitability for surgery. You also can comment on treatments that would make the patient a better candidate for surgery and plan for post-surgery psychiatric morbidities.

Key elements

Major mental illness. Without adequate treatment, major mood disorders can make a patient unable to undergo surgery. In addition, these types of surgeries are substantial life events that can trigger mood episodes. Educate patients about early signs of relapse and suggest a plan of action for treatment. A patient with an uncontrolled psychotic disorder and poor social support and/or case management is not a good candidate for surgery.

Substance use. Patients with active substance dependence are poor candidates for major surgeries unless they receive substance abuse treatment. During evaluation, motivational interviewing can help guide a patient toward treatment. Ensure that patients whose substance dependence is in remission have adequate support and treatment plans to prevent relapse.

Capacity to make decisions is based on the nature of the procedure and the patient’s ability to understand the process and risk vs benefits. The threshold for capacity can vary based on the procedure and the risks.²

Treatment adherence requires compliance with close medical follow-up, complicated medications, or lifestyle changes. A history of compliance with medical directives, medications, and appointments is important. Collateral information from the surgical team or caregivers can be helpful.

Coping style and strategies. Quiz the patient about internal and external resources they have used to cope with stress. A pattern of decompensation to using primitive defense mechanisms to handle stress suggests that the patient may have a personality disorder and might be a poor surgical candidate. Ability to use relatively mature defense strategies in stressful times suggests a good candidate.

Safety. Active suicidal or homicidal ideation is problematic in patients seeking major surgical interventions. Ensure that the stress of the surgery will not trigger dangerous behaviors. A history of frequent self-harm or impulsive suicidality suggests the that patient may have an unstable axis I or II disorder and might be a poor candidate for major surgery without further treatment.

FDA-approved for maintenance treatment of bipolar I disorder, lamotrigine is more effective than lithium for preventing depressive relapses. Lamotrigine combined with lithium, carbamazepine, or valproate provides good protection against recurrences of mania and depression.

Unlike selective serotonin reuptake inhibitors and other antidepressants, lamotrigine does not appear to increase risk of hypomania or mania in bipolar patients.¹ Unlike valproate and lithium, it is weight-neutral and requires no serum level monitoring.² Although lamotrigine’s slow titration and prolonged period until reaching therapeutic effect limits its efficacy as monotherapy in an inpatient setting, the drug can be initiated along with quicker acting agents in the hospital and then titrated after discharge. This strategy allows close monitoring during initial exposure.

Consider lamotrigine as an adjunct for treatment-resistant major depression.³ It is useful for treating aggression and agitation in patients with traumatic brain injury⁴ or dementia.⁵ Borderline personality disorder patients treated with lamotrigine may show less affective lability, impulsivity, or aggression.^6,7 Lamotrigine can act synergistically with clozapine in some patients with refractory schizophrenia.⁸

Metabolism and drug interactions

Lamotrigine is metabolized via glucuronidation and eliminated renally. Other drugs metabolized by glucuronidation could interact with lamotrigine (Table).⁹

Table

Drug interactions associated with lamotrigine

Adverse reactions

Lamotrigine is well tolerated chronically, with fewer adverse effects than other mood stabilizers. Serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in 0.08% to 0.13% of patients treated with lamotrigine for bipolar disorder or other mood disorders.⁹ The risk of developing a skin rash within 2 to 8 weeks of therapy necessitates starting with a low dose, usually 25 mg/d, and gradually titrating.^2,9

The FDA added a warning about increased risk of suicidality to the labeling of all anticonvulsants, regardless of indication.¹⁰ In a meta-analysis of 199 trials, for every 530 patients treated with anticonvulsants there was 1 additional case of suicidality—not completed suicide.¹⁰ Inform patients and their families about the potential risk for increased suicidality and document this discussion of risk vs benefit. All patients should be monitored for worsening depression or suicidal thoughts or behavior throughout treatment.

Other potential side effects occurring in at least 5% of patients receiving lamotrigine include somnolence, headache, rash, and the dose-related side effects of nausea, vomiting, dizziness, ataxia, blurred vision, and diplopia.⁹

FDA-approved for maintenance treatment of bipolar I disorder, lamotrigine is more effective than lithium for preventing depressive relapses. Lamotrigine combined with lithium, carbamazepine, or valproate provides good protection against recurrences of mania and depression.

Unlike selective serotonin reuptake inhibitors and other antidepressants, lamotrigine does not appear to increase risk of hypomania or mania in bipolar patients.¹ Unlike valproate and lithium, it is weight-neutral and requires no serum level monitoring.² Although lamotrigine’s slow titration and prolonged period until reaching therapeutic effect limits its efficacy as monotherapy in an inpatient setting, the drug can be initiated along with quicker acting agents in the hospital and then titrated after discharge. This strategy allows close monitoring during initial exposure.

Consider lamotrigine as an adjunct for treatment-resistant major depression.³ It is useful for treating aggression and agitation in patients with traumatic brain injury⁴ or dementia.⁵ Borderline personality disorder patients treated with lamotrigine may show less affective lability, impulsivity, or aggression.^6,7 Lamotrigine can act synergistically with clozapine in some patients with refractory schizophrenia.⁸

Metabolism and drug interactions

Lamotrigine is metabolized via glucuronidation and eliminated renally. Other drugs metabolized by glucuronidation could interact with lamotrigine (Table).⁹

Table

Drug interactions associated with lamotrigine

Adverse reactions

Lamotrigine is well tolerated chronically, with fewer adverse effects than other mood stabilizers. Serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in 0.08% to 0.13% of patients treated with lamotrigine for bipolar disorder or other mood disorders.⁹ The risk of developing a skin rash within 2 to 8 weeks of therapy necessitates starting with a low dose, usually 25 mg/d, and gradually titrating.^2,9

The FDA added a warning about increased risk of suicidality to the labeling of all anticonvulsants, regardless of indication.¹⁰ In a meta-analysis of 199 trials, for every 530 patients treated with anticonvulsants there was 1 additional case of suicidality—not completed suicide.¹⁰ Inform patients and their families about the potential risk for increased suicidality and document this discussion of risk vs benefit. All patients should be monitored for worsening depression or suicidal thoughts or behavior throughout treatment.

Other potential side effects occurring in at least 5% of patients receiving lamotrigine include somnolence, headache, rash, and the dose-related side effects of nausea, vomiting, dizziness, ataxia, blurred vision, and diplopia.⁹

FDA-approved for maintenance treatment of bipolar I disorder, lamotrigine is more effective than lithium for preventing depressive relapses. Lamotrigine combined with lithium, carbamazepine, or valproate provides good protection against recurrences of mania and depression.

Unlike selective serotonin reuptake inhibitors and other antidepressants, lamotrigine does not appear to increase risk of hypomania or mania in bipolar patients.¹ Unlike valproate and lithium, it is weight-neutral and requires no serum level monitoring.² Although lamotrigine’s slow titration and prolonged period until reaching therapeutic effect limits its efficacy as monotherapy in an inpatient setting, the drug can be initiated along with quicker acting agents in the hospital and then titrated after discharge. This strategy allows close monitoring during initial exposure.

Consider lamotrigine as an adjunct for treatment-resistant major depression.³ It is useful for treating aggression and agitation in patients with traumatic brain injury⁴ or dementia.⁵ Borderline personality disorder patients treated with lamotrigine may show less affective lability, impulsivity, or aggression.^6,7 Lamotrigine can act synergistically with clozapine in some patients with refractory schizophrenia.⁸

Metabolism and drug interactions

Lamotrigine is metabolized via glucuronidation and eliminated renally. Other drugs metabolized by glucuronidation could interact with lamotrigine (Table).⁹

Table

Drug interactions associated with lamotrigine

Adverse reactions

Lamotrigine is well tolerated chronically, with fewer adverse effects than other mood stabilizers. Serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in 0.08% to 0.13% of patients treated with lamotrigine for bipolar disorder or other mood disorders.⁹ The risk of developing a skin rash within 2 to 8 weeks of therapy necessitates starting with a low dose, usually 25 mg/d, and gradually titrating.^2,9

The FDA added a warning about increased risk of suicidality to the labeling of all anticonvulsants, regardless of indication.¹⁰ In a meta-analysis of 199 trials, for every 530 patients treated with anticonvulsants there was 1 additional case of suicidality—not completed suicide.¹⁰ Inform patients and their families about the potential risk for increased suicidality and document this discussion of risk vs benefit. All patients should be monitored for worsening depression or suicidal thoughts or behavior throughout treatment.

Other potential side effects occurring in at least 5% of patients receiving lamotrigine include somnolence, headache, rash, and the dose-related side effects of nausea, vomiting, dizziness, ataxia, blurred vision, and diplopia.⁹

Breast cancer is the most widespread cancer effecting women in the United States.¹ The high prevalence and inherent “cost” of breast cancer mandates physicians to be aware of effective screening tools, existing guidelines, and potential adverse effects.

Mammography screening and improvements in breast cancer treatments have contributed to improved survival rates, but^2,3 mammography screening has declined since 2000. Potential reasons for this decrease include:

• poor access to medical care
• fear of radiation exposure
• concern of undesirable test results
• anticipated pain
• misconceptions of cancer risk
• changes in recommendations regarding mammography screening.

Patients with psychiatric illnesses are less likely to receive mammography screening.^4,5 Cancer patients with schizophrenia, particularly women with breast cancer, have an increased risk of mortality.⁶

Risk assessment

Age, genetic predisposition, and factors that affect endogenous estrogen exposure such as early menarche, late menopause, and nulliparity are among the most important breast cancer risk factors (Table 1). Explore these and other risk factors with your patient before making screening recommendations.

Tools such as the Breast Cancer Risk Assessment Tool (BCRAT) can assist in stratifying your patient’s risk. The BCRAT, available at www.cancer.gov/bcrisktool, takes into account, age, race, family history, and previous breast abnormalities. Women at average risk for breast cancer include those with an estimated lifetime risk of <15%. Women with an estimated lifetime risk of 15% to 20% are at moderate risk. Women >20% are at high risk and should consider more intensive screening (Table 2).^7,8

Other examples of high-risk features include chest radiation therapy (eg, for Hodgkin’s lymphoma) between age 10 to 30 or a breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) mutation carried by the patient or a first-degree family member, which can leave patients more susceptible to breast cancer.

Table 1

Breast cancer risk factors

Breast cancer screening

Choice of screening is guided by an individualized risk assessment. For women with average risk for breast cancer, the major components of breast cancer screening are clinical breast examination (CBE) and screening mammography.

Breast self-examination is not routinely recommended by expert groups. The American Cancer Society (ACS) recommends that clinicians discuss the benefits and limitations of breast self-exam with patients. The National Comprehensive Cancer Network (NCCN) recommends that women maintain breast health awareness but no longer advocates instruction in self-examination.

CBE by a trained provider, when coupled to routine screening mammography, may add modest benefit in terms of detecting cancer. The ACS and the NCCN suggest CBE along with annual mammography for all women starting at age 40.

Mammography has been to shown to reduce breast cancer mortality.⁸ A United States Preventive Services Task Force (USPSTF) review found statistically significant reductions in breast cancer mortality for women age 39 to 69.⁹

Because the USPSTF found a small net benefit of screening mammography in women age 40 to 49, their recent guidelines recommend against routine mammograms for this age group. Instead, the USPSTF suggests that screening be based on individualized risk assessment and discussion of the benefits and risks (false positive tests, overdiagnosis, and psychological harms) of screening.¹⁰ Other groups continue to recommend annual mammography starting at age 40 for women at average risk (Table 2).

MRI is more sensitive screening than mammography and the combination of MRI and routine mammograms is more sensitive than either test alone. In 2007, the ACS recommended annual breast MRI screening in addition to mammogram for women at high risk for breast cancer (Table 2). For women with moderately increased risk (15% to 20% lifetime) there is insufficient evidence to recommend for or against MRI for screening, but one may consider it on a case-by-case basis; for example, for women with personal history of breast cancer, atypical hyperplasia, or with mammographically dense breasts.

Table 2

American Cancer Society breast cancer screening recommendations

Potential harms

Potential mammography harms include the possibility of a false positive result, anxiety as one awaits the test result, and anticipation of discomfort associated with the procedure. There also is the potential for “overdiagnosis” or detection of a cancer that would not have adversely impacted the patient if it had not been discovered. There is also a small risk of radiation exposure from repeated mammograms, but this has not been firmly established in the literature.

False-positive results—an abnormal finding on mammogram that does not result in a breast cancer diagnosis—is a significant issue. One study estimated that 11% of screening mammograms return abnormal findings that lead to additional workup, the majority (90%) of which ultimately result in benign diagnoses.¹¹ Workup often leads to additional mammograms, ultrasound, breast MRI, and invasive procedures such as needle biopsies. False-positive mammograms have been associated with increased symptoms of depression and anxiety.¹² Patients may be more apprehensive about breast cancer following a false-positive result, but this does not appear to lead to chronic anxiety.¹³

The vulnerability of patients experiencing psychiatric illness coupled with the potential psychological consequences of breast cancer make it imperative that psychiatrists remain up-to-date on breast cancer screening guidelines. Reported poor adherence to screening recommendations for mammography may increase the burden of illness and mortality from breast cancer in individuals with mental illness.

Conversations about health maintenance measures always should include careful discussion of the benefits and potential harms associated with the recommended screening tools. Because psychiatrists work closely with patients who may be less likely to undergo mammography, it is important to provide support and advocate for access to health care screening.

Related Resource

• National Cancer Institute. www.cancer.gov.

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Table 3

Number needed to screen (NNS) with mammography to prevent 1 breast cancer death