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TMS may bring remission in bipolar depression

HOLLYWOOD, FLA. – Transcranial magnetic stimulation shows promise in highly treatment-resistant bipolar depression, a small observational study suggested.

Most studies of transcranial magnetic stimulation (TMS) have focused on treatment of major depressive disorder, the indication for which this noninvasive device therapy has Food and Drug Administration approval. TMS also is under study for the treatment of headaches, as well as for improvement of the negative symptoms of schizophrenia.

Yet little work has been done on TMS for bipolar depression, even though a pressing need exists for new treatment options for this often highly disruptive mood disorder. Antidepressant medications are often ineffective or can trigger a switch to a manic or hypomanic episode, Dr. William S. Gilmer noted at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Dr. William Gilmer

He reported on 10 patients with bipolar II disorder and 4 who met criteria for bipolar disorder not otherwise specified. All had complicated nonpsychotic depression. All were refractory to and/or intolerant of multiple antidepressant agents during their current episode; indeed, the patients had previously been on a mean of 6.4 antidepressant drugs during this episode, which had already lasted more than 18 months in 9 of 14 cases. Four patients were previous nonresponders to ECT. None of the subjects had bipolar activation symptoms such as grandiosity, nocturnal alertness, or agitation at baseline, according to Dr. Gilmer, associate professor of clinical psychiatry and behavioral sciences at Northwestern University, Chicago.

After an extended period during which he attempted to optimize the participants’ medications, including reducing benzodiazepines and increasing mood-stabilizing drugs if necessary, all patients underwent high-frequency TMS at 10-Hz over the left dorsolateral prefrontal cortex 5 days per week according to the standard procedure using the NeuroStar device marketed by Neuronetics.

Nine of 14 patients achieved a clinically meaningful antidepressant response to TMS, as defined by at least a 50% reduction in scores on the Quick Inventory of Depressive Symptomatology (QIDS-16 SR) from an initial mean baseline of 18.9. A mean of 24.6 sessions was required. Four patients achieved and maintained remission, as defined by a QIDS-16 SR score below 6; this required a mean of 24.8 TMS sessions, followed by a taper phase.

Two of the four previous nonresponders to ECT achieved full remission on TMS, and a third had a significant response.

Although there were no study dropouts, seven patients experienced bipolar activation symptoms during TMS therapy that required drug therapy. Of note, four of five TMS nonresponders experienced clinically significant activation symptoms, compared with just three of nine TMS responders. Thus, the emergence of activation symptoms during TMS may turn out to be a predictor of poor outcome. This is a possibility warranting further study in controlled trials aimed at establishing optimal TMS treatment parameters in bipolar depression, the psychiatrist suggested.

Dr. Gilmer is on the speakers’ bureau for Neuronetics.

[email protected]

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HOLLYWOOD, FLA. – Transcranial magnetic stimulation shows promise in highly treatment-resistant bipolar depression, a small observational study suggested.

Most studies of transcranial magnetic stimulation (TMS) have focused on treatment of major depressive disorder, the indication for which this noninvasive device therapy has Food and Drug Administration approval. TMS also is under study for the treatment of headaches, as well as for improvement of the negative symptoms of schizophrenia.

Yet little work has been done on TMS for bipolar depression, even though a pressing need exists for new treatment options for this often highly disruptive mood disorder. Antidepressant medications are often ineffective or can trigger a switch to a manic or hypomanic episode, Dr. William S. Gilmer noted at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Dr. William Gilmer

He reported on 10 patients with bipolar II disorder and 4 who met criteria for bipolar disorder not otherwise specified. All had complicated nonpsychotic depression. All were refractory to and/or intolerant of multiple antidepressant agents during their current episode; indeed, the patients had previously been on a mean of 6.4 antidepressant drugs during this episode, which had already lasted more than 18 months in 9 of 14 cases. Four patients were previous nonresponders to ECT. None of the subjects had bipolar activation symptoms such as grandiosity, nocturnal alertness, or agitation at baseline, according to Dr. Gilmer, associate professor of clinical psychiatry and behavioral sciences at Northwestern University, Chicago.

After an extended period during which he attempted to optimize the participants’ medications, including reducing benzodiazepines and increasing mood-stabilizing drugs if necessary, all patients underwent high-frequency TMS at 10-Hz over the left dorsolateral prefrontal cortex 5 days per week according to the standard procedure using the NeuroStar device marketed by Neuronetics.

Nine of 14 patients achieved a clinically meaningful antidepressant response to TMS, as defined by at least a 50% reduction in scores on the Quick Inventory of Depressive Symptomatology (QIDS-16 SR) from an initial mean baseline of 18.9. A mean of 24.6 sessions was required. Four patients achieved and maintained remission, as defined by a QIDS-16 SR score below 6; this required a mean of 24.8 TMS sessions, followed by a taper phase.

Two of the four previous nonresponders to ECT achieved full remission on TMS, and a third had a significant response.

Although there were no study dropouts, seven patients experienced bipolar activation symptoms during TMS therapy that required drug therapy. Of note, four of five TMS nonresponders experienced clinically significant activation symptoms, compared with just three of nine TMS responders. Thus, the emergence of activation symptoms during TMS may turn out to be a predictor of poor outcome. This is a possibility warranting further study in controlled trials aimed at establishing optimal TMS treatment parameters in bipolar depression, the psychiatrist suggested.

Dr. Gilmer is on the speakers’ bureau for Neuronetics.

[email protected]

HOLLYWOOD, FLA. – Transcranial magnetic stimulation shows promise in highly treatment-resistant bipolar depression, a small observational study suggested.

Most studies of transcranial magnetic stimulation (TMS) have focused on treatment of major depressive disorder, the indication for which this noninvasive device therapy has Food and Drug Administration approval. TMS also is under study for the treatment of headaches, as well as for improvement of the negative symptoms of schizophrenia.

Yet little work has been done on TMS for bipolar depression, even though a pressing need exists for new treatment options for this often highly disruptive mood disorder. Antidepressant medications are often ineffective or can trigger a switch to a manic or hypomanic episode, Dr. William S. Gilmer noted at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Dr. William Gilmer

He reported on 10 patients with bipolar II disorder and 4 who met criteria for bipolar disorder not otherwise specified. All had complicated nonpsychotic depression. All were refractory to and/or intolerant of multiple antidepressant agents during their current episode; indeed, the patients had previously been on a mean of 6.4 antidepressant drugs during this episode, which had already lasted more than 18 months in 9 of 14 cases. Four patients were previous nonresponders to ECT. None of the subjects had bipolar activation symptoms such as grandiosity, nocturnal alertness, or agitation at baseline, according to Dr. Gilmer, associate professor of clinical psychiatry and behavioral sciences at Northwestern University, Chicago.

After an extended period during which he attempted to optimize the participants’ medications, including reducing benzodiazepines and increasing mood-stabilizing drugs if necessary, all patients underwent high-frequency TMS at 10-Hz over the left dorsolateral prefrontal cortex 5 days per week according to the standard procedure using the NeuroStar device marketed by Neuronetics.

Nine of 14 patients achieved a clinically meaningful antidepressant response to TMS, as defined by at least a 50% reduction in scores on the Quick Inventory of Depressive Symptomatology (QIDS-16 SR) from an initial mean baseline of 18.9. A mean of 24.6 sessions was required. Four patients achieved and maintained remission, as defined by a QIDS-16 SR score below 6; this required a mean of 24.8 TMS sessions, followed by a taper phase.

Two of the four previous nonresponders to ECT achieved full remission on TMS, and a third had a significant response.

Although there were no study dropouts, seven patients experienced bipolar activation symptoms during TMS therapy that required drug therapy. Of note, four of five TMS nonresponders experienced clinically significant activation symptoms, compared with just three of nine TMS responders. Thus, the emergence of activation symptoms during TMS may turn out to be a predictor of poor outcome. This is a possibility warranting further study in controlled trials aimed at establishing optimal TMS treatment parameters in bipolar depression, the psychiatrist suggested.

Dr. Gilmer is on the speakers’ bureau for Neuronetics.

[email protected]

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TMS may bring remission in bipolar depression
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Major finding: Nine of 14 patients with highly treatment-resistant bipolar depression achieved a clinically meaningful antidepressant response to transcranial magnetic stimulation, including 4 who reached and maintained remission. Two of the four in remission were prior nonresponders to ECT.

Data source: This observational study was a naturalistic case series with no control group. Patients had been unresponsive to and/or intolerant of a mean of 6.4 antidepressant medications during their current episode of bipolar depression, which had been ongoing for more than 18 months in nine cases.

Disclosures: Dr. Gilmer is on the speakers’ bureau for Neuronetics, which markets the transcranial magnetic stimulation device used in the investigation.