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Treatment response rates for psychotic bipolar depression similar to those without
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
[email protected]
On Twitter @whitneymcknight
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
[email protected]
On Twitter @whitneymcknight
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
[email protected]
On Twitter @whitneymcknight
AT THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Patients with psychotic or nonpsychotic bipolar depression responded equally well to lithium and quetiapine when compared with response rates in patients without bipolar depression.
Data source: A secondary analysis of 32 patients from a multisite, randomized, controlled trial of 482 patients with bipolar disorder I or bipolar II and psychosis, assigned to receive either lithium or quetiapine for 6 months.
Disclosures: Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
First trimester lithium exposure ups risk of cardiac malformations
Cardiac malformations are three times more likely to occur in infants exposed to lithium during the first trimester of gestation than in unexposed infants.
The increased risk could account for one additional cardiac malformation per 100 live births, Elisabetta Patorno, MD, and her colleagues wrote in the June 8 issue of the New England Journal of Medicine (2017;376:2245-54).
Dr. Patorno’s study is the largest conducted since then. It comprised more than 1.3 million pregnancies included in the U.S. Medicaid Analytic eXtract database during 2000-2010. Of these, 663 had first trimester lithium exposure. These were compared with 1,945 pregnancies with first trimester exposure to lamotrigine, another mood stabilizer, and to the remaining 1.3 million pregnancies unexposed to either drug.
There were 16 cardiac malformations in the lithium group (2.41%); 27 in the lamotrigine group (1.39%); and 15,251 in the unexposed group (1.15%). Lithium conferred a 65% increased risk of cardiac defect, compared with unexposed pregnancies. It more than doubled the risk when compared with lamotrigine-exposed pregnancies (risk ratio, 2.25).
The risk was dose dependent, however, with an 11% increase associated with 600 mg/day or less and a 60% increase associated with 601-900 mg/day. Infants exposed to more than 900 mg per day in the first trimester, however, were more than 300% more likely to have a cardiac malformation (RR, 3.22).
The investigators also examined the association of lithium with cardiac defects consistent with Ebstein’s anomaly. Lithium more than doubled the risk, compared with unexposed infants (RR, 2.66). This risk was also dose dependent; all of the right ventricular outflow defects occurred in infants exposed to more than 600 mg/day.
Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.
[email protected]
On Twitter @Alz_gal
Cardiac malformations are three times more likely to occur in infants exposed to lithium during the first trimester of gestation than in unexposed infants.
The increased risk could account for one additional cardiac malformation per 100 live births, Elisabetta Patorno, MD, and her colleagues wrote in the June 8 issue of the New England Journal of Medicine (2017;376:2245-54).
Dr. Patorno’s study is the largest conducted since then. It comprised more than 1.3 million pregnancies included in the U.S. Medicaid Analytic eXtract database during 2000-2010. Of these, 663 had first trimester lithium exposure. These were compared with 1,945 pregnancies with first trimester exposure to lamotrigine, another mood stabilizer, and to the remaining 1.3 million pregnancies unexposed to either drug.
There were 16 cardiac malformations in the lithium group (2.41%); 27 in the lamotrigine group (1.39%); and 15,251 in the unexposed group (1.15%). Lithium conferred a 65% increased risk of cardiac defect, compared with unexposed pregnancies. It more than doubled the risk when compared with lamotrigine-exposed pregnancies (risk ratio, 2.25).
The risk was dose dependent, however, with an 11% increase associated with 600 mg/day or less and a 60% increase associated with 601-900 mg/day. Infants exposed to more than 900 mg per day in the first trimester, however, were more than 300% more likely to have a cardiac malformation (RR, 3.22).
The investigators also examined the association of lithium with cardiac defects consistent with Ebstein’s anomaly. Lithium more than doubled the risk, compared with unexposed infants (RR, 2.66). This risk was also dose dependent; all of the right ventricular outflow defects occurred in infants exposed to more than 600 mg/day.
Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.
[email protected]
On Twitter @Alz_gal
Cardiac malformations are three times more likely to occur in infants exposed to lithium during the first trimester of gestation than in unexposed infants.
The increased risk could account for one additional cardiac malformation per 100 live births, Elisabetta Patorno, MD, and her colleagues wrote in the June 8 issue of the New England Journal of Medicine (2017;376:2245-54).
Dr. Patorno’s study is the largest conducted since then. It comprised more than 1.3 million pregnancies included in the U.S. Medicaid Analytic eXtract database during 2000-2010. Of these, 663 had first trimester lithium exposure. These were compared with 1,945 pregnancies with first trimester exposure to lamotrigine, another mood stabilizer, and to the remaining 1.3 million pregnancies unexposed to either drug.
There were 16 cardiac malformations in the lithium group (2.41%); 27 in the lamotrigine group (1.39%); and 15,251 in the unexposed group (1.15%). Lithium conferred a 65% increased risk of cardiac defect, compared with unexposed pregnancies. It more than doubled the risk when compared with lamotrigine-exposed pregnancies (risk ratio, 2.25).
The risk was dose dependent, however, with an 11% increase associated with 600 mg/day or less and a 60% increase associated with 601-900 mg/day. Infants exposed to more than 900 mg per day in the first trimester, however, were more than 300% more likely to have a cardiac malformation (RR, 3.22).
The investigators also examined the association of lithium with cardiac defects consistent with Ebstein’s anomaly. Lithium more than doubled the risk, compared with unexposed infants (RR, 2.66). This risk was also dose dependent; all of the right ventricular outflow defects occurred in infants exposed to more than 600 mg/day.
Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.
[email protected]
On Twitter @Alz_gal
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: The dose-dependent increased risks ranged from 11% to more than 300%, compared with unexposed pregnancies.
Data source: The Medicaid database review comprised more than 1.3 million pregnancies.
Disclosures: Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.
Herb–drug interactions: Caution patients when changing supplements
Ms. X, age 41, has a history of bipolar disorder and presents with extreme sleepiness, constipation with mild abdominal cramping, occasional dizziness, and “palpitations.” Although usually she is quite articulate, Ms. X seems to have trouble describing her symptoms and reports that they have been worsening over 4 to 6 days. She is worried because she is making mistakes at work and repeatedly misunderstanding directions.
Ms. X has a family history of hyperlipidemia, heart disease, and diabetes, and she has been employing a healthy diet, exercise, and use of supplements for cardiovascular health since her early 20s. Her medication regimen includes lithium, 600 mg, twice a day, quetiapine, 1,200 mg/d, a multivitamin and mineral tablet once a day, a brand name garlic supplement (garlic powder, 300 mg, vitamin C, 80 mg, vitamin E, 20 IU, vitamin A, 2,640 IU) twice a day, and fish oil, 2 g/d, at bedtime. Lithium levels consistently have been 0.8 to 0.9 mEq/L for the last 3 years.
Factors of drug–supplement interactions
Because an interaction is possible doesn’t always mean that a drug and an offending botanical cannot be used together. With awareness and planning, possible interactions can be safely managed (Table 1). Such was the case of Ms. X, who was stable on a higher-than-usual dosage of quetiapine (average target is 600 mg/d for bipolar disorder) because of presumed moderate enzyme induction by the brand name garlic supplement. Ms. X did not want to stop taking this supplement when she started quetiapine. Although garlic is listed as a possible moderate cytochrome P450 (CYP) 3A4 inducer, there is conflicting evidence.1 Ms. X’s clinician advised her to avoid changes in dosage, because it could affect her quetiapine levels. However, the change in the botanical preparation from dried, powdered garlic to garlic oil likely removed the CYP3A4 enzyme induction, leading to a lower rate of metabolism and accumulation of the drug to toxic levels. 
Drug metabolism. Practitioners are increasingly aware that St. John’s wort can significantly affect concomitantly administered drug levels by induction of the CYP isoenzyme 3A4 and more resources are listing this same possible induction for garlic.1 However, what is less understood is the extent to which different preparations of the same plant possess different chemical profiles (Table 2).
Clinical studies with different garlic preparations—dried powder, aqueous extracts, deodorized preparations, oils—have demonstrated diverse and highly variable results in tests of effects on CYP isoenzymes and other metabolism activities.
Drug absorption. Small differences in amounts of vitamins in the supplement are unlikely to be clinically significant, but the addition of piperine could be affecting quetiapine absorption. Piperine, a constituent of black pepper and long pepper, is used in Ayurvedic medicine for:
- pain
- influenza
- rheumatoid arthritis
- asthma
- loss of appetite
- stimulating peristalsis.6
Animal studies have demonstrated anti-inflammatory, anticonvulsant, anticarcinogenic, and antioxidant effects, as well as stimulation of digestion via digestive enzyme secretion and increased gastromotility.3,6
Because piperine is known to increase intestinal absorption by various mechanisms, it often is added to botanical medicines to increase bioavailability of active components. BioPerine is a 95% piperine extract marketed to be included in vitamin and herbal supplements for that purpose.3 This allows use of lower dosages to achieve outcomes, which, for expensive botanicals, could be a cost savings for the manufacturer. Studies examining piperine’s influence on drug absorption have demonstrated significant increases in carbamazepine, rifampin, phenytoin, nevirapine, and many other drugs.
In addition to increased absorption, piperine seems to be a non-specific general inhibitor of CYP isoenzymes; IV phenytoin levels also were higher among test participants.6,8 Piperine reduces intestinal glucuronidation via uridine 5’-diphospho-glucuronosyltransferase inhibition, and the small or moderate effects on lithium levels seem to be the result of diuretic activities.3,7
Patients often are motivated to control at least 1 aspect of their medical treatment, such as the supplements they choose to take. Being open to patient use of non-harmful or low-risk supplements, even when they are unlikely to have any medicinal benefit, helps preserve a relationship in which patients are more likely to consider your recommendation to avoid a harmful or high-risk supplement.
Related Resources
1. Natural Medicines Database. Garlic monograph. http://naturaldatabase.therapeuticresearch.com. Accessed May 1, 2017.
2. Wanwimolruk S, Prachayasittikul V. Cytochrome P450 enzyme mediated herbal drug interactions (part 1). EXCLI J. 2014;13:347-391.
3. Colalto C. Herbal interactions on absorption of drugs: mechanism of action and clinical risk assessment. Pharmacol Res. 2010;62(3):207-227.
4. Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St. John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging. 2005;22(6):525-539.
5. Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2003;55(2):199-202.
6. Meghwal M, Goswami TK. Piper nigrum and piperine: an update. Phytother Res. 2013;27(8):1121-1130.
7. Natural Medicines Database. Black pepper monograph. https://www.naturalmedicines.therapeuticresearch.com. Accessed May 1, 2017.
8. Zhou S, Lim LY, Chowbay B. Herbal modulation of p-glycoprotein. Drug Metab Rev. 2004;36(1):57-104.
9. Chinta G, Syed B, Coumar MS, et al. Piperine: a comprehensive review of pre-clinical and clinical investigations. Curr Bioact Compd. 2015;11(3):156-169.
Ms. X, age 41, has a history of bipolar disorder and presents with extreme sleepiness, constipation with mild abdominal cramping, occasional dizziness, and “palpitations.” Although usually she is quite articulate, Ms. X seems to have trouble describing her symptoms and reports that they have been worsening over 4 to 6 days. She is worried because she is making mistakes at work and repeatedly misunderstanding directions.
Ms. X has a family history of hyperlipidemia, heart disease, and diabetes, and she has been employing a healthy diet, exercise, and use of supplements for cardiovascular health since her early 20s. Her medication regimen includes lithium, 600 mg, twice a day, quetiapine, 1,200 mg/d, a multivitamin and mineral tablet once a day, a brand name garlic supplement (garlic powder, 300 mg, vitamin C, 80 mg, vitamin E, 20 IU, vitamin A, 2,640 IU) twice a day, and fish oil, 2 g/d, at bedtime. Lithium levels consistently have been 0.8 to 0.9 mEq/L for the last 3 years.
Factors of drug–supplement interactions
Because an interaction is possible doesn’t always mean that a drug and an offending botanical cannot be used together. With awareness and planning, possible interactions can be safely managed (Table 1). Such was the case of Ms. X, who was stable on a higher-than-usual dosage of quetiapine (average target is 600 mg/d for bipolar disorder) because of presumed moderate enzyme induction by the brand name garlic supplement. Ms. X did not want to stop taking this supplement when she started quetiapine. Although garlic is listed as a possible moderate cytochrome P450 (CYP) 3A4 inducer, there is conflicting evidence.1 Ms. X’s clinician advised her to avoid changes in dosage, because it could affect her quetiapine levels. However, the change in the botanical preparation from dried, powdered garlic to garlic oil likely removed the CYP3A4 enzyme induction, leading to a lower rate of metabolism and accumulation of the drug to toxic levels.
Drug metabolism. Practitioners are increasingly aware that St. John’s wort can significantly affect concomitantly administered drug levels by induction of the CYP isoenzyme 3A4 and more resources are listing this same possible induction for garlic.1 However, what is less understood is the extent to which different preparations of the same plant possess different chemical profiles (Table 2).
Clinical studies with different garlic preparations—dried powder, aqueous extracts, deodorized preparations, oils—have demonstrated diverse and highly variable results in tests of effects on CYP isoenzymes and other metabolism activities.
Drug absorption. Small differences in amounts of vitamins in the supplement are unlikely to be clinically significant, but the addition of piperine could be affecting quetiapine absorption. Piperine, a constituent of black pepper and long pepper, is used in Ayurvedic medicine for:
- pain
- influenza
- rheumatoid arthritis
- asthma
- loss of appetite
- stimulating peristalsis.6
Animal studies have demonstrated anti-inflammatory, anticonvulsant, anticarcinogenic, and antioxidant effects, as well as stimulation of digestion via digestive enzyme secretion and increased gastromotility.3,6
Because piperine is known to increase intestinal absorption by various mechanisms, it often is added to botanical medicines to increase bioavailability of active components. BioPerine is a 95% piperine extract marketed to be included in vitamin and herbal supplements for that purpose.3 This allows use of lower dosages to achieve outcomes, which, for expensive botanicals, could be a cost savings for the manufacturer. Studies examining piperine’s influence on drug absorption have demonstrated significant increases in carbamazepine, rifampin, phenytoin, nevirapine, and many other drugs.
In addition to increased absorption, piperine seems to be a non-specific general inhibitor of CYP isoenzymes; IV phenytoin levels also were higher among test participants.6,8 Piperine reduces intestinal glucuronidation via uridine 5’-diphospho-glucuronosyltransferase inhibition, and the small or moderate effects on lithium levels seem to be the result of diuretic activities.3,7
Patients often are motivated to control at least 1 aspect of their medical treatment, such as the supplements they choose to take. Being open to patient use of non-harmful or low-risk supplements, even when they are unlikely to have any medicinal benefit, helps preserve a relationship in which patients are more likely to consider your recommendation to avoid a harmful or high-risk supplement.
Related Resources
Ms. X, age 41, has a history of bipolar disorder and presents with extreme sleepiness, constipation with mild abdominal cramping, occasional dizziness, and “palpitations.” Although usually she is quite articulate, Ms. X seems to have trouble describing her symptoms and reports that they have been worsening over 4 to 6 days. She is worried because she is making mistakes at work and repeatedly misunderstanding directions.
Ms. X has a family history of hyperlipidemia, heart disease, and diabetes, and she has been employing a healthy diet, exercise, and use of supplements for cardiovascular health since her early 20s. Her medication regimen includes lithium, 600 mg, twice a day, quetiapine, 1,200 mg/d, a multivitamin and mineral tablet once a day, a brand name garlic supplement (garlic powder, 300 mg, vitamin C, 80 mg, vitamin E, 20 IU, vitamin A, 2,640 IU) twice a day, and fish oil, 2 g/d, at bedtime. Lithium levels consistently have been 0.8 to 0.9 mEq/L for the last 3 years.
Factors of drug–supplement interactions
Because an interaction is possible doesn’t always mean that a drug and an offending botanical cannot be used together. With awareness and planning, possible interactions can be safely managed (Table 1). Such was the case of Ms. X, who was stable on a higher-than-usual dosage of quetiapine (average target is 600 mg/d for bipolar disorder) because of presumed moderate enzyme induction by the brand name garlic supplement. Ms. X did not want to stop taking this supplement when she started quetiapine. Although garlic is listed as a possible moderate cytochrome P450 (CYP) 3A4 inducer, there is conflicting evidence.1 Ms. X’s clinician advised her to avoid changes in dosage, because it could affect her quetiapine levels. However, the change in the botanical preparation from dried, powdered garlic to garlic oil likely removed the CYP3A4 enzyme induction, leading to a lower rate of metabolism and accumulation of the drug to toxic levels.
Drug metabolism. Practitioners are increasingly aware that St. John’s wort can significantly affect concomitantly administered drug levels by induction of the CYP isoenzyme 3A4 and more resources are listing this same possible induction for garlic.1 However, what is less understood is the extent to which different preparations of the same plant possess different chemical profiles (Table 2).
Clinical studies with different garlic preparations—dried powder, aqueous extracts, deodorized preparations, oils—have demonstrated diverse and highly variable results in tests of effects on CYP isoenzymes and other metabolism activities.
Drug absorption. Small differences in amounts of vitamins in the supplement are unlikely to be clinically significant, but the addition of piperine could be affecting quetiapine absorption. Piperine, a constituent of black pepper and long pepper, is used in Ayurvedic medicine for:
- pain
- influenza
- rheumatoid arthritis
- asthma
- loss of appetite
- stimulating peristalsis.6
Animal studies have demonstrated anti-inflammatory, anticonvulsant, anticarcinogenic, and antioxidant effects, as well as stimulation of digestion via digestive enzyme secretion and increased gastromotility.3,6
Because piperine is known to increase intestinal absorption by various mechanisms, it often is added to botanical medicines to increase bioavailability of active components. BioPerine is a 95% piperine extract marketed to be included in vitamin and herbal supplements for that purpose.3 This allows use of lower dosages to achieve outcomes, which, for expensive botanicals, could be a cost savings for the manufacturer. Studies examining piperine’s influence on drug absorption have demonstrated significant increases in carbamazepine, rifampin, phenytoin, nevirapine, and many other drugs.
In addition to increased absorption, piperine seems to be a non-specific general inhibitor of CYP isoenzymes; IV phenytoin levels also were higher among test participants.6,8 Piperine reduces intestinal glucuronidation via uridine 5’-diphospho-glucuronosyltransferase inhibition, and the small or moderate effects on lithium levels seem to be the result of diuretic activities.3,7
Patients often are motivated to control at least 1 aspect of their medical treatment, such as the supplements they choose to take. Being open to patient use of non-harmful or low-risk supplements, even when they are unlikely to have any medicinal benefit, helps preserve a relationship in which patients are more likely to consider your recommendation to avoid a harmful or high-risk supplement.
Related Resources
1. Natural Medicines Database. Garlic monograph. http://naturaldatabase.therapeuticresearch.com. Accessed May 1, 2017.
2. Wanwimolruk S, Prachayasittikul V. Cytochrome P450 enzyme mediated herbal drug interactions (part 1). EXCLI J. 2014;13:347-391.
3. Colalto C. Herbal interactions on absorption of drugs: mechanism of action and clinical risk assessment. Pharmacol Res. 2010;62(3):207-227.
4. Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St. John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging. 2005;22(6):525-539.
5. Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2003;55(2):199-202.
6. Meghwal M, Goswami TK. Piper nigrum and piperine: an update. Phytother Res. 2013;27(8):1121-1130.
7. Natural Medicines Database. Black pepper monograph. https://www.naturalmedicines.therapeuticresearch.com. Accessed May 1, 2017.
8. Zhou S, Lim LY, Chowbay B. Herbal modulation of p-glycoprotein. Drug Metab Rev. 2004;36(1):57-104.
9. Chinta G, Syed B, Coumar MS, et al. Piperine: a comprehensive review of pre-clinical and clinical investigations. Curr Bioact Compd. 2015;11(3):156-169.
1. Natural Medicines Database. Garlic monograph. http://naturaldatabase.therapeuticresearch.com. Accessed May 1, 2017.
2. Wanwimolruk S, Prachayasittikul V. Cytochrome P450 enzyme mediated herbal drug interactions (part 1). EXCLI J. 2014;13:347-391.
3. Colalto C. Herbal interactions on absorption of drugs: mechanism of action and clinical risk assessment. Pharmacol Res. 2010;62(3):207-227.
4. Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St. John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging. 2005;22(6):525-539.
5. Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2003;55(2):199-202.
6. Meghwal M, Goswami TK. Piper nigrum and piperine: an update. Phytother Res. 2013;27(8):1121-1130.
7. Natural Medicines Database. Black pepper monograph. https://www.naturalmedicines.therapeuticresearch.com. Accessed May 1, 2017.
8. Zhou S, Lim LY, Chowbay B. Herbal modulation of p-glycoprotein. Drug Metab Rev. 2004;36(1):57-104.
9. Chinta G, Syed B, Coumar MS, et al. Piperine: a comprehensive review of pre-clinical and clinical investigations. Curr Bioact Compd. 2015;11(3):156-169.
Psychological account of Robert Lowell’s life is magnificent
Robert Lowell knew civic valor. Sixteen times and more he had been down on his knees in madness, he said. Sixteen times and more he had gotten up. He had gone back to his work, entered back into life. He had faced down uncertainty and madness, had created new forms when pushed to stay with the old, had brought back imaginative order from chaos. It was a different kind of courage, this civic courage, and the rules of engagement were unclear. Lowell’s life, as his daughter observed, was a messy one, difficult for him and for those who knew him. But it was lived with iron, and often with grace. He kept always in the front of his mind what he thought he ought to be, even when he couldn’t be it; he believed in what his country could be, even if it wasn’t. He worked hard at his art.
–Kay Redfield Jamison, PhD, in “Robert Lowell, Setting the River on Fire: A Study of Genius, Mania, and Character” (New York: Alfred A. Knopf, 2017).
Lowell, who lived from 1917 to 1977, was a two-time Pulitzer Prize winner, deemed to be the greatest American poet of his time. He studied the classics and was obsessed with Napoleon as a child, and he drew on the work of other great poets and classicists as influences for his own work. I must confess, I came to this psychological study having never read the work of Robert Lowell. My only familiarity with the poet came directly from the author. I heard Dr. Jamison, a professor of psychiatry at Johns Hopkins University, Baltimore, speak several years ago at the Johns Hopkins Annual Mood Disorders Symposium about her then work-in-progress as she was researching this book. What I heard was intriguing enough that I was eager to read and review a long and solid book about a great poet whose work I had never read.
As I began “Setting The River On Fire,” my first thought was that the writing itself was astounding. Dr. Jamison’s words flow, her metaphors never fall flat or feel artificial, the ride itself is lovely. I looked for a few lines to quote as an example, and I was left at a standstill. One line was more gracious than the next. I finally settled on the quote I used at the beginning of this piece, benignly chosen from page 403 because it encapsulated not just the beautiful writing but a synopsis of who Lowell was and what he had achieved, set in the context of attempted differentiation between the man, the madness, and the interplay of the two.
Dr. Jamison’s research on Lowell’s life is nothing short of astounding and was clearly a labor that took both sustained passion and years of her time. Dr. Jamison quoted the poet at length. She is an expert on his many volumes of poetry and prose, as well as his life and loves – three marriages and many intimate friendships – documented through letters and conversations. In addition, she quoted many other poets as examples of how their work influenced Lowell. Beyond the literature and correspondence, Dr. Jamison interviewed those who knew Lowell well. She unearthed his medical and psychiatric records, and she plotted out the course of his life in an uncanny way, linking so much of his work to the ebbs and flows of his illness. My only “criticism” of the book would be in how extensive it is. She sometimes makes a point by quoting several sources, each of whom drive at the same idea. It makes for very strong rhetoric.
His second wife, Elizabeth Hardwick, had a striking understanding of his illness as a biological disorder beyond his control. Her sympathy for his behavior as a product of illness allowed her to tolerate actions that many people would not, even with our current day emphasis on disease states, including sexual indiscretions. His friends, too, saw the uncharacteristic chaos of his manias as the result of a state of illness, and, as such, as forgivable. These were often not subtle indiscretions: Jamison describes intense delusional states, combative behavior, police with straightjackets, often at very public and professional events worldwide. If psychoanalytic thinking weighed in on an understanding of Lowell’s motivations, Dr. Jamison did not include it in her study of Lowell, and she makes a point at the end of saying that she focused on his illness and did not include the content of psychotherapy notes. Still, I was struck by the understanding of his depressions and manias as a state of illness by lay people in his life and thought that, given the time period, it was noteworthy.
On a similar vein, I wondered if Lowell could live his life now as he lived his life then. A crucial arena for his career was Harvard College, where he returned over and over to teach. Dr. Jamison says that Lowell lectured in an acutely psychotic and disorganized state. She says that, while students clamored to take his classes, so, too, they were afraid of him. I cannot quite imagine that, in our world of “trigger warnings,” microaggressions, and college safe spaces, we might ever allow an openly ill genius to reign in a classroom of students. I am never certain if we are aimed forward or backward in our struggle against stigma, and “Setting The River On Fire” may be one more example in which we have lost ground in a quest for tolerance.
Once again, Dr. Jamison pulled me into her world. “Setting The River On Fire” is no one’s version of a light or happy read, it is a serious study of an intensely brilliant and often desperately ill poet – and it does not disappoint.
Dr. Miller, who practices in Baltimore, is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care,” (Baltimore: Johns Hopkins University Press, 2016).
Robert Lowell knew civic valor. Sixteen times and more he had been down on his knees in madness, he said. Sixteen times and more he had gotten up. He had gone back to his work, entered back into life. He had faced down uncertainty and madness, had created new forms when pushed to stay with the old, had brought back imaginative order from chaos. It was a different kind of courage, this civic courage, and the rules of engagement were unclear. Lowell’s life, as his daughter observed, was a messy one, difficult for him and for those who knew him. But it was lived with iron, and often with grace. He kept always in the front of his mind what he thought he ought to be, even when he couldn’t be it; he believed in what his country could be, even if it wasn’t. He worked hard at his art.
–Kay Redfield Jamison, PhD, in “Robert Lowell, Setting the River on Fire: A Study of Genius, Mania, and Character” (New York: Alfred A. Knopf, 2017).
Lowell, who lived from 1917 to 1977, was a two-time Pulitzer Prize winner, deemed to be the greatest American poet of his time. He studied the classics and was obsessed with Napoleon as a child, and he drew on the work of other great poets and classicists as influences for his own work. I must confess, I came to this psychological study having never read the work of Robert Lowell. My only familiarity with the poet came directly from the author. I heard Dr. Jamison, a professor of psychiatry at Johns Hopkins University, Baltimore, speak several years ago at the Johns Hopkins Annual Mood Disorders Symposium about her then work-in-progress as she was researching this book. What I heard was intriguing enough that I was eager to read and review a long and solid book about a great poet whose work I had never read.
As I began “Setting The River On Fire,” my first thought was that the writing itself was astounding. Dr. Jamison’s words flow, her metaphors never fall flat or feel artificial, the ride itself is lovely. I looked for a few lines to quote as an example, and I was left at a standstill. One line was more gracious than the next. I finally settled on the quote I used at the beginning of this piece, benignly chosen from page 403 because it encapsulated not just the beautiful writing but a synopsis of who Lowell was and what he had achieved, set in the context of attempted differentiation between the man, the madness, and the interplay of the two.
Dr. Jamison’s research on Lowell’s life is nothing short of astounding and was clearly a labor that took both sustained passion and years of her time. Dr. Jamison quoted the poet at length. She is an expert on his many volumes of poetry and prose, as well as his life and loves – three marriages and many intimate friendships – documented through letters and conversations. In addition, she quoted many other poets as examples of how their work influenced Lowell. Beyond the literature and correspondence, Dr. Jamison interviewed those who knew Lowell well. She unearthed his medical and psychiatric records, and she plotted out the course of his life in an uncanny way, linking so much of his work to the ebbs and flows of his illness. My only “criticism” of the book would be in how extensive it is. She sometimes makes a point by quoting several sources, each of whom drive at the same idea. It makes for very strong rhetoric.
His second wife, Elizabeth Hardwick, had a striking understanding of his illness as a biological disorder beyond his control. Her sympathy for his behavior as a product of illness allowed her to tolerate actions that many people would not, even with our current day emphasis on disease states, including sexual indiscretions. His friends, too, saw the uncharacteristic chaos of his manias as the result of a state of illness, and, as such, as forgivable. These were often not subtle indiscretions: Jamison describes intense delusional states, combative behavior, police with straightjackets, often at very public and professional events worldwide. If psychoanalytic thinking weighed in on an understanding of Lowell’s motivations, Dr. Jamison did not include it in her study of Lowell, and she makes a point at the end of saying that she focused on his illness and did not include the content of psychotherapy notes. Still, I was struck by the understanding of his depressions and manias as a state of illness by lay people in his life and thought that, given the time period, it was noteworthy.
On a similar vein, I wondered if Lowell could live his life now as he lived his life then. A crucial arena for his career was Harvard College, where he returned over and over to teach. Dr. Jamison says that Lowell lectured in an acutely psychotic and disorganized state. She says that, while students clamored to take his classes, so, too, they were afraid of him. I cannot quite imagine that, in our world of “trigger warnings,” microaggressions, and college safe spaces, we might ever allow an openly ill genius to reign in a classroom of students. I am never certain if we are aimed forward or backward in our struggle against stigma, and “Setting The River On Fire” may be one more example in which we have lost ground in a quest for tolerance.
Once again, Dr. Jamison pulled me into her world. “Setting The River On Fire” is no one’s version of a light or happy read, it is a serious study of an intensely brilliant and often desperately ill poet – and it does not disappoint.
Dr. Miller, who practices in Baltimore, is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care,” (Baltimore: Johns Hopkins University Press, 2016).
Robert Lowell knew civic valor. Sixteen times and more he had been down on his knees in madness, he said. Sixteen times and more he had gotten up. He had gone back to his work, entered back into life. He had faced down uncertainty and madness, had created new forms when pushed to stay with the old, had brought back imaginative order from chaos. It was a different kind of courage, this civic courage, and the rules of engagement were unclear. Lowell’s life, as his daughter observed, was a messy one, difficult for him and for those who knew him. But it was lived with iron, and often with grace. He kept always in the front of his mind what he thought he ought to be, even when he couldn’t be it; he believed in what his country could be, even if it wasn’t. He worked hard at his art.
–Kay Redfield Jamison, PhD, in “Robert Lowell, Setting the River on Fire: A Study of Genius, Mania, and Character” (New York: Alfred A. Knopf, 2017).
Lowell, who lived from 1917 to 1977, was a two-time Pulitzer Prize winner, deemed to be the greatest American poet of his time. He studied the classics and was obsessed with Napoleon as a child, and he drew on the work of other great poets and classicists as influences for his own work. I must confess, I came to this psychological study having never read the work of Robert Lowell. My only familiarity with the poet came directly from the author. I heard Dr. Jamison, a professor of psychiatry at Johns Hopkins University, Baltimore, speak several years ago at the Johns Hopkins Annual Mood Disorders Symposium about her then work-in-progress as she was researching this book. What I heard was intriguing enough that I was eager to read and review a long and solid book about a great poet whose work I had never read.
As I began “Setting The River On Fire,” my first thought was that the writing itself was astounding. Dr. Jamison’s words flow, her metaphors never fall flat or feel artificial, the ride itself is lovely. I looked for a few lines to quote as an example, and I was left at a standstill. One line was more gracious than the next. I finally settled on the quote I used at the beginning of this piece, benignly chosen from page 403 because it encapsulated not just the beautiful writing but a synopsis of who Lowell was and what he had achieved, set in the context of attempted differentiation between the man, the madness, and the interplay of the two.
Dr. Jamison’s research on Lowell’s life is nothing short of astounding and was clearly a labor that took both sustained passion and years of her time. Dr. Jamison quoted the poet at length. She is an expert on his many volumes of poetry and prose, as well as his life and loves – three marriages and many intimate friendships – documented through letters and conversations. In addition, she quoted many other poets as examples of how their work influenced Lowell. Beyond the literature and correspondence, Dr. Jamison interviewed those who knew Lowell well. She unearthed his medical and psychiatric records, and she plotted out the course of his life in an uncanny way, linking so much of his work to the ebbs and flows of his illness. My only “criticism” of the book would be in how extensive it is. She sometimes makes a point by quoting several sources, each of whom drive at the same idea. It makes for very strong rhetoric.
His second wife, Elizabeth Hardwick, had a striking understanding of his illness as a biological disorder beyond his control. Her sympathy for his behavior as a product of illness allowed her to tolerate actions that many people would not, even with our current day emphasis on disease states, including sexual indiscretions. His friends, too, saw the uncharacteristic chaos of his manias as the result of a state of illness, and, as such, as forgivable. These were often not subtle indiscretions: Jamison describes intense delusional states, combative behavior, police with straightjackets, often at very public and professional events worldwide. If psychoanalytic thinking weighed in on an understanding of Lowell’s motivations, Dr. Jamison did not include it in her study of Lowell, and she makes a point at the end of saying that she focused on his illness and did not include the content of psychotherapy notes. Still, I was struck by the understanding of his depressions and manias as a state of illness by lay people in his life and thought that, given the time period, it was noteworthy.
On a similar vein, I wondered if Lowell could live his life now as he lived his life then. A crucial arena for his career was Harvard College, where he returned over and over to teach. Dr. Jamison says that Lowell lectured in an acutely psychotic and disorganized state. She says that, while students clamored to take his classes, so, too, they were afraid of him. I cannot quite imagine that, in our world of “trigger warnings,” microaggressions, and college safe spaces, we might ever allow an openly ill genius to reign in a classroom of students. I am never certain if we are aimed forward or backward in our struggle against stigma, and “Setting The River On Fire” may be one more example in which we have lost ground in a quest for tolerance.
Once again, Dr. Jamison pulled me into her world. “Setting The River On Fire” is no one’s version of a light or happy read, it is a serious study of an intensely brilliant and often desperately ill poet – and it does not disappoint.
Dr. Miller, who practices in Baltimore, is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care,” (Baltimore: Johns Hopkins University Press, 2016).
Is your patient’s valproic acid dosage too low or high? Adjust it with this equation
Valproic acid (VPA) often is used to treat mania in bipolar disorder, and it has a therapeutic range of 50 to 125 µg/mL of total serum concentration.1 VPA binds highly to albumin, resulting in free drug concentrations (5 to 15 mg/L) that are responsible for its therapeutic effect.2 Monitoring total VPA levels in patients with hypoalbuminemia could reveal seemingly subtherapeutic VPA levels, which could lead to unnecessary dosage adjustments or drug toxicity. Hermida et al3 devised a correction equation to normalize total VPA serum concentrations <75 µg/mL in patients with hypoalbuminemia (Table 1, Box).
We present a case employing this equation in a patient
Case
Ms. T, age 75, is admitted to the hospital with delusional, paranoid, assaultive, and combative behavior. By applying Ms. T’s baseline lab findings (Table 2) to the equation, a normalized total VPA level and estimated free VPA level of 70 µg/mL and 7 µg/mL, respectively, can be approximated. These estimates fall within the therapeutic range and are validated by the measured free VPA level of 9 µg/mL.
VPA serum levels should be assessed 2 to 4 days after initiation or dosage adjustments.1 Also, consider patient-specific goals and intended clinical effect when adjusting VPA dosage. In practice settings, where free VPA levels are not routinely monitored or are cost prohibitive, this equation can guide clinical decision-making.3
1. Depakote [divalproex sodium]. North Chicago, IL: AbbVie Inc; 2016.
2. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull. 2003;37(suppl 2):25-42.
3. Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97(4):489-493.
Valproic acid (VPA) often is used to treat mania in bipolar disorder, and it has a therapeutic range of 50 to 125 µg/mL of total serum concentration.1 VPA binds highly to albumin, resulting in free drug concentrations (5 to 15 mg/L) that are responsible for its therapeutic effect.2 Monitoring total VPA levels in patients with hypoalbuminemia could reveal seemingly subtherapeutic VPA levels, which could lead to unnecessary dosage adjustments or drug toxicity. Hermida et al3 devised a correction equation to normalize total VPA serum concentrations <75 µg/mL in patients with hypoalbuminemia (Table 1, Box).
We present a case employing this equation in a patient
Case
Ms. T, age 75, is admitted to the hospital with delusional, paranoid, assaultive, and combative behavior. By applying Ms. T’s baseline lab findings (Table 2) to the equation, a normalized total VPA level and estimated free VPA level of 70 µg/mL and 7 µg/mL, respectively, can be approximated. These estimates fall within the therapeutic range and are validated by the measured free VPA level of 9 µg/mL.
VPA serum levels should be assessed 2 to 4 days after initiation or dosage adjustments.1 Also, consider patient-specific goals and intended clinical effect when adjusting VPA dosage. In practice settings, where free VPA levels are not routinely monitored or are cost prohibitive, this equation can guide clinical decision-making.3
Valproic acid (VPA) often is used to treat mania in bipolar disorder, and it has a therapeutic range of 50 to 125 µg/mL of total serum concentration.1 VPA binds highly to albumin, resulting in free drug concentrations (5 to 15 mg/L) that are responsible for its therapeutic effect.2 Monitoring total VPA levels in patients with hypoalbuminemia could reveal seemingly subtherapeutic VPA levels, which could lead to unnecessary dosage adjustments or drug toxicity. Hermida et al3 devised a correction equation to normalize total VPA serum concentrations <75 µg/mL in patients with hypoalbuminemia (Table 1, Box).
We present a case employing this equation in a patient
Case
Ms. T, age 75, is admitted to the hospital with delusional, paranoid, assaultive, and combative behavior. By applying Ms. T’s baseline lab findings (Table 2) to the equation, a normalized total VPA level and estimated free VPA level of 70 µg/mL and 7 µg/mL, respectively, can be approximated. These estimates fall within the therapeutic range and are validated by the measured free VPA level of 9 µg/mL.
VPA serum levels should be assessed 2 to 4 days after initiation or dosage adjustments.1 Also, consider patient-specific goals and intended clinical effect when adjusting VPA dosage. In practice settings, where free VPA levels are not routinely monitored or are cost prohibitive, this equation can guide clinical decision-making.3
1. Depakote [divalproex sodium]. North Chicago, IL: AbbVie Inc; 2016.
2. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull. 2003;37(suppl 2):25-42.
3. Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97(4):489-493.
1. Depakote [divalproex sodium]. North Chicago, IL: AbbVie Inc; 2016.
2. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull. 2003;37(suppl 2):25-42.
3. Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97(4):489-493.
Minimizing use of antipsychotics
Treating psychopathology in developmentally disabled tricky
LAS VEGAS – Individuals with intellectual disability experience behavioral and psychiatric illness at higher rates than the general population, according to Bryan H. King, MD.
“Increasingly, these individuals are showing up in all of our clinical practices,” Dr. King said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “In this area, it’s not so much that the population doesn’t experience psychiatric illness, but the diagnosis can be challenging because the presentation of symptoms may be different. For someone who can’t articulate whether they’re feeling anxious, fearful, or nervous, it’s more challenging to make a diagnosis.”
More than 10 years ago, researchers from the University of North Carolina at Chapel Hill compared health disparities between adults with developmental disabilities in North Carolina and adults in the state with other disabilities and adults without disabilities (Public Health Rep. 2004;114[4]:418-26). They found those in the developmental disability group had a similar or greater risk of having high blood pressure, cardiovascular disease, diabetes, and chronic pain, compared with nondisabled adults. In addition, 24% of adults in the developmental disability group reported having either no one to talk to about personal things or often felt lonely.
A more recent, large national study found that, compared with adults with no autism diagnoses, those diagnosed with autism had significantly increased rates for all psychiatric disorders, including depression, anxiety, bipolar disorder, obsessive-compulsive disorder, schizophrenia (a more than 20-fold increased rate), and suicide attempts (Autism. 2015;19[7]:814-23). In addition, nearly all medical conditions such as obesity and dyslipidemia were significantly more common in adults with autism.
Results from a separate study of 371 adults with intellectual disabilities found that 40% had at least one mental health disorder and 45% had at least one moderate or severe behavior problem (Soc Psychiatry Psychiatr Epidemiol. 2016;51:767-76). In addition, the highest ratios of unmet to met need were found with respect to sexuality issues and with respect to mental health problems.
Once a diagnosis is made, Dr. King said patients who have developmental disabilities should be treated in the same way as patients who do not. “There is a tremendous amount of heterogeneity in this population,” he said. “If you are confident that you have someone before you who has depression, the treatment for depression is going to proceed in the same ways it does for someone without the condition. Let that guide the way for medications you are going to use.”
In a recent edition of Current Opinion in Psychiatry, authors Na Young Ji, MD, and Robert L. Findling, MD, reviewed current evidence-based pharmacotherapy options for mental health problems in people with intellectual disability (Curr Opin Psychiatry. 2016;29:103-25). Their five key points were:
1. “Antipsychotics, particularly risperidone, appear to be effective in reducing problem behaviors associated with intellectual disability.
2. “For attention-deficit/hyperactivity disorder symptoms, methylphenidate has been shown to be effective, and atomoxetine and alpha-agonists might be beneficial.
3. “Lithium might be effective in reducing aggression. Evidence for the use of antiepileptic drugs, anxiolytics, and naltrexone for management of problem behaviors is insufficient to draw conclusions.
4. “Antidepressants are often poorly tolerated and do not appear to be effective in decreasing repetitive or stereotypic behaviors associated with intellectual disability.
5. “Melatonin appears to improve sleep in people with intellectual disability.”
Dr. King noted that the data for using lithium in people with intellectual disability “are very old. There’s been nothing recent to help us fine-tune the indications.” He said naltrexone is among the best studied in this population, “especially for self-injurious behavior. The two large placebo-controlled trials were negative. In my own clinical experience, I have not seen it helpful.”
Dr. King disclosed that he has received research funding from the National Institutes of Health, Janssen, and Roche. He also is a consultant for Care Management Technologies and Neurotrope.
LAS VEGAS – Individuals with intellectual disability experience behavioral and psychiatric illness at higher rates than the general population, according to Bryan H. King, MD.
“Increasingly, these individuals are showing up in all of our clinical practices,” Dr. King said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “In this area, it’s not so much that the population doesn’t experience psychiatric illness, but the diagnosis can be challenging because the presentation of symptoms may be different. For someone who can’t articulate whether they’re feeling anxious, fearful, or nervous, it’s more challenging to make a diagnosis.”
More than 10 years ago, researchers from the University of North Carolina at Chapel Hill compared health disparities between adults with developmental disabilities in North Carolina and adults in the state with other disabilities and adults without disabilities (Public Health Rep. 2004;114[4]:418-26). They found those in the developmental disability group had a similar or greater risk of having high blood pressure, cardiovascular disease, diabetes, and chronic pain, compared with nondisabled adults. In addition, 24% of adults in the developmental disability group reported having either no one to talk to about personal things or often felt lonely.
A more recent, large national study found that, compared with adults with no autism diagnoses, those diagnosed with autism had significantly increased rates for all psychiatric disorders, including depression, anxiety, bipolar disorder, obsessive-compulsive disorder, schizophrenia (a more than 20-fold increased rate), and suicide attempts (Autism. 2015;19[7]:814-23). In addition, nearly all medical conditions such as obesity and dyslipidemia were significantly more common in adults with autism.
Results from a separate study of 371 adults with intellectual disabilities found that 40% had at least one mental health disorder and 45% had at least one moderate or severe behavior problem (Soc Psychiatry Psychiatr Epidemiol. 2016;51:767-76). In addition, the highest ratios of unmet to met need were found with respect to sexuality issues and with respect to mental health problems.
Once a diagnosis is made, Dr. King said patients who have developmental disabilities should be treated in the same way as patients who do not. “There is a tremendous amount of heterogeneity in this population,” he said. “If you are confident that you have someone before you who has depression, the treatment for depression is going to proceed in the same ways it does for someone without the condition. Let that guide the way for medications you are going to use.”
In a recent edition of Current Opinion in Psychiatry, authors Na Young Ji, MD, and Robert L. Findling, MD, reviewed current evidence-based pharmacotherapy options for mental health problems in people with intellectual disability (Curr Opin Psychiatry. 2016;29:103-25). Their five key points were:
1. “Antipsychotics, particularly risperidone, appear to be effective in reducing problem behaviors associated with intellectual disability.
2. “For attention-deficit/hyperactivity disorder symptoms, methylphenidate has been shown to be effective, and atomoxetine and alpha-agonists might be beneficial.
3. “Lithium might be effective in reducing aggression. Evidence for the use of antiepileptic drugs, anxiolytics, and naltrexone for management of problem behaviors is insufficient to draw conclusions.
4. “Antidepressants are often poorly tolerated and do not appear to be effective in decreasing repetitive or stereotypic behaviors associated with intellectual disability.
5. “Melatonin appears to improve sleep in people with intellectual disability.”
Dr. King noted that the data for using lithium in people with intellectual disability “are very old. There’s been nothing recent to help us fine-tune the indications.” He said naltrexone is among the best studied in this population, “especially for self-injurious behavior. The two large placebo-controlled trials were negative. In my own clinical experience, I have not seen it helpful.”
Dr. King disclosed that he has received research funding from the National Institutes of Health, Janssen, and Roche. He also is a consultant for Care Management Technologies and Neurotrope.
LAS VEGAS – Individuals with intellectual disability experience behavioral and psychiatric illness at higher rates than the general population, according to Bryan H. King, MD.
“Increasingly, these individuals are showing up in all of our clinical practices,” Dr. King said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “In this area, it’s not so much that the population doesn’t experience psychiatric illness, but the diagnosis can be challenging because the presentation of symptoms may be different. For someone who can’t articulate whether they’re feeling anxious, fearful, or nervous, it’s more challenging to make a diagnosis.”
More than 10 years ago, researchers from the University of North Carolina at Chapel Hill compared health disparities between adults with developmental disabilities in North Carolina and adults in the state with other disabilities and adults without disabilities (Public Health Rep. 2004;114[4]:418-26). They found those in the developmental disability group had a similar or greater risk of having high blood pressure, cardiovascular disease, diabetes, and chronic pain, compared with nondisabled adults. In addition, 24% of adults in the developmental disability group reported having either no one to talk to about personal things or often felt lonely.
A more recent, large national study found that, compared with adults with no autism diagnoses, those diagnosed with autism had significantly increased rates for all psychiatric disorders, including depression, anxiety, bipolar disorder, obsessive-compulsive disorder, schizophrenia (a more than 20-fold increased rate), and suicide attempts (Autism. 2015;19[7]:814-23). In addition, nearly all medical conditions such as obesity and dyslipidemia were significantly more common in adults with autism.
Results from a separate study of 371 adults with intellectual disabilities found that 40% had at least one mental health disorder and 45% had at least one moderate or severe behavior problem (Soc Psychiatry Psychiatr Epidemiol. 2016;51:767-76). In addition, the highest ratios of unmet to met need were found with respect to sexuality issues and with respect to mental health problems.
Once a diagnosis is made, Dr. King said patients who have developmental disabilities should be treated in the same way as patients who do not. “There is a tremendous amount of heterogeneity in this population,” he said. “If you are confident that you have someone before you who has depression, the treatment for depression is going to proceed in the same ways it does for someone without the condition. Let that guide the way for medications you are going to use.”
In a recent edition of Current Opinion in Psychiatry, authors Na Young Ji, MD, and Robert L. Findling, MD, reviewed current evidence-based pharmacotherapy options for mental health problems in people with intellectual disability (Curr Opin Psychiatry. 2016;29:103-25). Their five key points were:
1. “Antipsychotics, particularly risperidone, appear to be effective in reducing problem behaviors associated with intellectual disability.
2. “For attention-deficit/hyperactivity disorder symptoms, methylphenidate has been shown to be effective, and atomoxetine and alpha-agonists might be beneficial.
3. “Lithium might be effective in reducing aggression. Evidence for the use of antiepileptic drugs, anxiolytics, and naltrexone for management of problem behaviors is insufficient to draw conclusions.
4. “Antidepressants are often poorly tolerated and do not appear to be effective in decreasing repetitive or stereotypic behaviors associated with intellectual disability.
5. “Melatonin appears to improve sleep in people with intellectual disability.”
Dr. King noted that the data for using lithium in people with intellectual disability “are very old. There’s been nothing recent to help us fine-tune the indications.” He said naltrexone is among the best studied in this population, “especially for self-injurious behavior. The two large placebo-controlled trials were negative. In my own clinical experience, I have not seen it helpful.”
Dr. King disclosed that he has received research funding from the National Institutes of Health, Janssen, and Roche. He also is a consultant for Care Management Technologies and Neurotrope.
EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE
SSRI activation in children, adolescents often misdiagnosed as bipolar
SAN FRANCISCO – It’s not uncommon for children to arrive at the Western Psychiatric Institute and Clinic in Pittsburgh with selective serotonin reuptake inhibitor activation that was misdiagnosed as bipolar disorder, according to Boris Birmaher, MD.
“We get many kids into our clinic with a diagnosis of bipolar because of this, and they are not bipolar. You have to be careful,” he said during a talk about pediatric depression at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
SSRIs activate about 5%-10% of children. There might be sleep problems, fast speech, hyperactivity, agitation, aggression, and even suicidality, he said.
Younger children and those with autism or developmental disabilities are particularly at risk. Occasionally, a child might be a slow metabolizer so that even low SSRI doses cause problems. “Once in a blue moon,” Dr. Birmaher said he will screen for genetic cytochrome P450 deficiency, especially if a child doesn’t seem able to tolerate medications in general, not just psychiatric ones. He’s found a few slow metabolizers over the years.
Psychiatrists also have to be careful when children and adolescents are tagged as “treatment resistant.” It’s important to teach parents what treatment resistance would actually look like for their child, so they don’t jump to conclusions and misdirect therapy, he said.
For example, when a child has been prescribed an SSRI for anxiety, parents might come in and say it’s not helping, when in fact they’re concerned about homework not getting done and restlessness in class. “There’s no treatment resistance. You teach the parent how to measure improvement of anxiety” and tackle the ADHD if it’s truly a problem, said Dr. Birmaher, also professor of psychiatry at the University of Pittsburgh.
If there really is SSRI treatment resistance, he said he first ensures that a maximum dose of the drug has been tried, so long as it’s tolerated. If it doesn’t work after 4-6 weeks, he’ll switch to another SSRI or selective norepinephrine reuptake inhibitor, or combination treatment with, for instance, bupropion (Wellbutrin) or an atypical antipsychotic, which are particularly helpful for irritability, even in small doses. Atypicals seem to take the edge off, he said.
It’s trial and error, since there aren’t much data in children to guide treatment. “The only thing I highly recommend is to make one change at a time. Sometimes we see kids who’ve had two or three changes at the same time.” In those cases, he said, it’s impossible to know what to blame if there are side effects or what to credit if depression improves.
Dr. Birmaher said he had no pharmaceutical industry ties.
SAN FRANCISCO – It’s not uncommon for children to arrive at the Western Psychiatric Institute and Clinic in Pittsburgh with selective serotonin reuptake inhibitor activation that was misdiagnosed as bipolar disorder, according to Boris Birmaher, MD.
“We get many kids into our clinic with a diagnosis of bipolar because of this, and they are not bipolar. You have to be careful,” he said during a talk about pediatric depression at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
SSRIs activate about 5%-10% of children. There might be sleep problems, fast speech, hyperactivity, agitation, aggression, and even suicidality, he said.
Younger children and those with autism or developmental disabilities are particularly at risk. Occasionally, a child might be a slow metabolizer so that even low SSRI doses cause problems. “Once in a blue moon,” Dr. Birmaher said he will screen for genetic cytochrome P450 deficiency, especially if a child doesn’t seem able to tolerate medications in general, not just psychiatric ones. He’s found a few slow metabolizers over the years.
Psychiatrists also have to be careful when children and adolescents are tagged as “treatment resistant.” It’s important to teach parents what treatment resistance would actually look like for their child, so they don’t jump to conclusions and misdirect therapy, he said.
For example, when a child has been prescribed an SSRI for anxiety, parents might come in and say it’s not helping, when in fact they’re concerned about homework not getting done and restlessness in class. “There’s no treatment resistance. You teach the parent how to measure improvement of anxiety” and tackle the ADHD if it’s truly a problem, said Dr. Birmaher, also professor of psychiatry at the University of Pittsburgh.
If there really is SSRI treatment resistance, he said he first ensures that a maximum dose of the drug has been tried, so long as it’s tolerated. If it doesn’t work after 4-6 weeks, he’ll switch to another SSRI or selective norepinephrine reuptake inhibitor, or combination treatment with, for instance, bupropion (Wellbutrin) or an atypical antipsychotic, which are particularly helpful for irritability, even in small doses. Atypicals seem to take the edge off, he said.
It’s trial and error, since there aren’t much data in children to guide treatment. “The only thing I highly recommend is to make one change at a time. Sometimes we see kids who’ve had two or three changes at the same time.” In those cases, he said, it’s impossible to know what to blame if there are side effects or what to credit if depression improves.
Dr. Birmaher said he had no pharmaceutical industry ties.
SAN FRANCISCO – It’s not uncommon for children to arrive at the Western Psychiatric Institute and Clinic in Pittsburgh with selective serotonin reuptake inhibitor activation that was misdiagnosed as bipolar disorder, according to Boris Birmaher, MD.
“We get many kids into our clinic with a diagnosis of bipolar because of this, and they are not bipolar. You have to be careful,” he said during a talk about pediatric depression at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
SSRIs activate about 5%-10% of children. There might be sleep problems, fast speech, hyperactivity, agitation, aggression, and even suicidality, he said.
Younger children and those with autism or developmental disabilities are particularly at risk. Occasionally, a child might be a slow metabolizer so that even low SSRI doses cause problems. “Once in a blue moon,” Dr. Birmaher said he will screen for genetic cytochrome P450 deficiency, especially if a child doesn’t seem able to tolerate medications in general, not just psychiatric ones. He’s found a few slow metabolizers over the years.
Psychiatrists also have to be careful when children and adolescents are tagged as “treatment resistant.” It’s important to teach parents what treatment resistance would actually look like for their child, so they don’t jump to conclusions and misdirect therapy, he said.
For example, when a child has been prescribed an SSRI for anxiety, parents might come in and say it’s not helping, when in fact they’re concerned about homework not getting done and restlessness in class. “There’s no treatment resistance. You teach the parent how to measure improvement of anxiety” and tackle the ADHD if it’s truly a problem, said Dr. Birmaher, also professor of psychiatry at the University of Pittsburgh.
If there really is SSRI treatment resistance, he said he first ensures that a maximum dose of the drug has been tried, so long as it’s tolerated. If it doesn’t work after 4-6 weeks, he’ll switch to another SSRI or selective norepinephrine reuptake inhibitor, or combination treatment with, for instance, bupropion (Wellbutrin) or an atypical antipsychotic, which are particularly helpful for irritability, even in small doses. Atypicals seem to take the edge off, he said.
It’s trial and error, since there aren’t much data in children to guide treatment. “The only thing I highly recommend is to make one change at a time. Sometimes we see kids who’ve had two or three changes at the same time.” In those cases, he said, it’s impossible to know what to blame if there are side effects or what to credit if depression improves.
Dr. Birmaher said he had no pharmaceutical industry ties.
EXPERT ANALYSIS AT THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Pills to powder: An updated clinician’s reference for crushable psychotropics
Many patients experience difficulty swallowing pills, for various reasons:
- discomfort (particularly pediatric and geriatric patients)
- postsurgical need for an alternate route of enteral intake (nasogastric tube, gastrostomy, jejunostomy)
- dysphagia due to a neurologic disorder (multiple sclerosis, impaired gag reflex, dementing processes)
- odynophagia (pain upon swallowing) due to gastroesophageal reflux or a structural abnormality
- a structural abnormality of the head or neck that impairs swallowing.1
If these difficulties are not addressed, they can interfere with medication adherence. In those instances, using an alternative dosage form or manipulating an available formulation might be required.
Crushing guidelines
There are limited data on crushed-form products and their impact on efficacy. Therefore, when patients have difficulty taking pills, switching to liquid solution or orally disintegrating forms is recommended. However, most psychotropics are available only as tablets or capsules. Patients can crush their pills immediately before administration for easier intake. The following are some general guidelines for doing so:2
- Scored tablets typically can be crushed.
- Crushing sublingual and buccal tablets can alter their effectiveness.
- Crushing sustained-release medications can eliminate the sustained-release action.3
- Enteric-coated medications should not be crushed, because this can alter drug absorption.
- Capsules generally can be opened to administer powdered contents, unless the capsule has time-release properties or an enteric coating.
The accompanying Table, organized by drug class, indicates whether a drug can be crushed to a powdered form, which usually is mixed with food or liquid for easier intake. The Table also lists liquid and orally disintegrating forms available, and other routes, including injectable immediate and long-acting formulations. Helping patients find a medication formulation that suits their needs strengthens adherence and the therapeutic relationship.
1. Schiele JT, Quinzler R, Klimm HD, et al. Difficulties swallowing solid oral dosage forms in a general practice population: prevalence, causes, and relationship to dosage forms. Eur J Clin Pharmacol. 2013;69(4): 937-948.
2. PL Detail-Document, Meds That Should Not Be Crushed. Pharmacist’s Letter/Prescriber’sLetter. July 2012.
3. Mitchell JF. Oral dosage forms that should not be crushed. http://www.ismp.org/tools/donotcrush.pdf. Updated January 2015. Accessed January 17, 2017.
Many patients experience difficulty swallowing pills, for various reasons:
- discomfort (particularly pediatric and geriatric patients)
- postsurgical need for an alternate route of enteral intake (nasogastric tube, gastrostomy, jejunostomy)
- dysphagia due to a neurologic disorder (multiple sclerosis, impaired gag reflex, dementing processes)
- odynophagia (pain upon swallowing) due to gastroesophageal reflux or a structural abnormality
- a structural abnormality of the head or neck that impairs swallowing.1
If these difficulties are not addressed, they can interfere with medication adherence. In those instances, using an alternative dosage form or manipulating an available formulation might be required.
Crushing guidelines
There are limited data on crushed-form products and their impact on efficacy. Therefore, when patients have difficulty taking pills, switching to liquid solution or orally disintegrating forms is recommended. However, most psychotropics are available only as tablets or capsules. Patients can crush their pills immediately before administration for easier intake. The following are some general guidelines for doing so:2
- Scored tablets typically can be crushed.
- Crushing sublingual and buccal tablets can alter their effectiveness.
- Crushing sustained-release medications can eliminate the sustained-release action.3
- Enteric-coated medications should not be crushed, because this can alter drug absorption.
- Capsules generally can be opened to administer powdered contents, unless the capsule has time-release properties or an enteric coating.
The accompanying Table, organized by drug class, indicates whether a drug can be crushed to a powdered form, which usually is mixed with food or liquid for easier intake. The Table also lists liquid and orally disintegrating forms available, and other routes, including injectable immediate and long-acting formulations. Helping patients find a medication formulation that suits their needs strengthens adherence and the therapeutic relationship.
Many patients experience difficulty swallowing pills, for various reasons:
- discomfort (particularly pediatric and geriatric patients)
- postsurgical need for an alternate route of enteral intake (nasogastric tube, gastrostomy, jejunostomy)
- dysphagia due to a neurologic disorder (multiple sclerosis, impaired gag reflex, dementing processes)
- odynophagia (pain upon swallowing) due to gastroesophageal reflux or a structural abnormality
- a structural abnormality of the head or neck that impairs swallowing.1
If these difficulties are not addressed, they can interfere with medication adherence. In those instances, using an alternative dosage form or manipulating an available formulation might be required.
Crushing guidelines
There are limited data on crushed-form products and their impact on efficacy. Therefore, when patients have difficulty taking pills, switching to liquid solution or orally disintegrating forms is recommended. However, most psychotropics are available only as tablets or capsules. Patients can crush their pills immediately before administration for easier intake. The following are some general guidelines for doing so:2
- Scored tablets typically can be crushed.
- Crushing sublingual and buccal tablets can alter their effectiveness.
- Crushing sustained-release medications can eliminate the sustained-release action.3
- Enteric-coated medications should not be crushed, because this can alter drug absorption.
- Capsules generally can be opened to administer powdered contents, unless the capsule has time-release properties or an enteric coating.
The accompanying Table, organized by drug class, indicates whether a drug can be crushed to a powdered form, which usually is mixed with food or liquid for easier intake. The Table also lists liquid and orally disintegrating forms available, and other routes, including injectable immediate and long-acting formulations. Helping patients find a medication formulation that suits their needs strengthens adherence and the therapeutic relationship.
1. Schiele JT, Quinzler R, Klimm HD, et al. Difficulties swallowing solid oral dosage forms in a general practice population: prevalence, causes, and relationship to dosage forms. Eur J Clin Pharmacol. 2013;69(4): 937-948.
2. PL Detail-Document, Meds That Should Not Be Crushed. Pharmacist’s Letter/Prescriber’sLetter. July 2012.
3. Mitchell JF. Oral dosage forms that should not be crushed. http://www.ismp.org/tools/donotcrush.pdf. Updated January 2015. Accessed January 17, 2017.
1. Schiele JT, Quinzler R, Klimm HD, et al. Difficulties swallowing solid oral dosage forms in a general practice population: prevalence, causes, and relationship to dosage forms. Eur J Clin Pharmacol. 2013;69(4): 937-948.
2. PL Detail-Document, Meds That Should Not Be Crushed. Pharmacist’s Letter/Prescriber’sLetter. July 2012.
3. Mitchell JF. Oral dosage forms that should not be crushed. http://www.ismp.org/tools/donotcrush.pdf. Updated January 2015. Accessed January 17, 2017.
Lower BDNF levels found in older adults with bipolar I
Older patients with bipolar I disorder appear to have lower serum levels of brain-deprived neurotrophic factor than similarly aged adults without bipolar I, a study showed.
At the beginning of the study, Aline T. Soares, MD, and her colleagues recruited 118 patients from clinics in the United States and Canada with bipolar disorder who were aged 50 and over and a similar control group of 76 healthy patients. Twenty-seven of the 118 patients had type II bipolar disorder, and 91 had type I bipolar disorder; all had been clinically euthymic for at least 4 weeks when they were evaluated, reported Dr. Soares of the department of internal medicine at the University of São Paulo (Brazil).
The results showed that patients positively identified with bipolar I disorder had lowered brain-deprived neurotrophic factor (BDNF) levels, compared with their control group counterparts. Lower levels of BDNF were not detected in those with bipolar II disorder, the investigators reported (Am J Geriatr Psychiatry. 2016 Aug;24[8]:596-601).
“Our study represents a continuation of the [bipolar disorder] and BDNF story: Prolonged bipolar illness appears to lead to decreased BDNF, even in the euthymic state,” Dr. Soares and her colleagues wrote. “This reduces the brain’s capacity for neurogenesis and neuroplasticity and theoretically increases the risk of hippocampal shrinkage, cognitive deficits, and dementia.”
Future studies are needed to look into how BDNF levels affect mood, cognitive abilities, and other areas of life related to bipolar disorder, they said.
Dr. Soares and her colleagues reported that they had no conflicts to disclose.
To read more about the study, click here.
Older patients with bipolar I disorder appear to have lower serum levels of brain-deprived neurotrophic factor than similarly aged adults without bipolar I, a study showed.
At the beginning of the study, Aline T. Soares, MD, and her colleagues recruited 118 patients from clinics in the United States and Canada with bipolar disorder who were aged 50 and over and a similar control group of 76 healthy patients. Twenty-seven of the 118 patients had type II bipolar disorder, and 91 had type I bipolar disorder; all had been clinically euthymic for at least 4 weeks when they were evaluated, reported Dr. Soares of the department of internal medicine at the University of São Paulo (Brazil).
The results showed that patients positively identified with bipolar I disorder had lowered brain-deprived neurotrophic factor (BDNF) levels, compared with their control group counterparts. Lower levels of BDNF were not detected in those with bipolar II disorder, the investigators reported (Am J Geriatr Psychiatry. 2016 Aug;24[8]:596-601).
“Our study represents a continuation of the [bipolar disorder] and BDNF story: Prolonged bipolar illness appears to lead to decreased BDNF, even in the euthymic state,” Dr. Soares and her colleagues wrote. “This reduces the brain’s capacity for neurogenesis and neuroplasticity and theoretically increases the risk of hippocampal shrinkage, cognitive deficits, and dementia.”
Future studies are needed to look into how BDNF levels affect mood, cognitive abilities, and other areas of life related to bipolar disorder, they said.
Dr. Soares and her colleagues reported that they had no conflicts to disclose.
To read more about the study, click here.
Older patients with bipolar I disorder appear to have lower serum levels of brain-deprived neurotrophic factor than similarly aged adults without bipolar I, a study showed.
At the beginning of the study, Aline T. Soares, MD, and her colleagues recruited 118 patients from clinics in the United States and Canada with bipolar disorder who were aged 50 and over and a similar control group of 76 healthy patients. Twenty-seven of the 118 patients had type II bipolar disorder, and 91 had type I bipolar disorder; all had been clinically euthymic for at least 4 weeks when they were evaluated, reported Dr. Soares of the department of internal medicine at the University of São Paulo (Brazil).
The results showed that patients positively identified with bipolar I disorder had lowered brain-deprived neurotrophic factor (BDNF) levels, compared with their control group counterparts. Lower levels of BDNF were not detected in those with bipolar II disorder, the investigators reported (Am J Geriatr Psychiatry. 2016 Aug;24[8]:596-601).
“Our study represents a continuation of the [bipolar disorder] and BDNF story: Prolonged bipolar illness appears to lead to decreased BDNF, even in the euthymic state,” Dr. Soares and her colleagues wrote. “This reduces the brain’s capacity for neurogenesis and neuroplasticity and theoretically increases the risk of hippocampal shrinkage, cognitive deficits, and dementia.”
Future studies are needed to look into how BDNF levels affect mood, cognitive abilities, and other areas of life related to bipolar disorder, they said.
Dr. Soares and her colleagues reported that they had no conflicts to disclose.
To read more about the study, click here.
FROM THE AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY