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Mania After Transcranial Magnetic Stimulation in PTSD

To the Editor: Hagit Cohen, Ph.D., et al. (1) recently reported the first randomized trial of different frequencies of transcranial magnetic stimulation versus placebo for posttraumatic stress disorder (PTSD), to our knowledge. This trial is comparable to a phase II dose-finding study in clinical drug development, during which assessment of safety and tolerability is also a main objective. The authors concluded that transcranial magnetic stimulation was generally well tolerated and that no serious side effects occurred. However, they also reported that two of 18 patients developed a manic episode after the third of 10 sessions of transcranial magnetic stimulation. In my opinion, a manic episode is a severe or even serious adverse event because it has a great impact on someone’s functioning, and it is a potentially life-threatening illness.

Mania has so far not been described as a side effect in trials of transcranial magnetic stimulation for unipolar depression (2) or for bipolar depression (3). This, in combination with the fact that mania is an uncommon symptom in PTSD, makes the occurrence of mania less likely to be the effect of chance and more likely to be an idiosyncratic side effect of right dorsolateral prefrontal transcranial magnetic stimulation in PTSD. To be able to further judge this, it would be relevant to know how severe these manic episodes were, how long they lasted, and how they were treated. It would also be important for the interpretation of the trial to know whether the treatment with transcranial magnetic stimulation was stopped as a consequence of the occurrence of mania. Finally, it would be relevant to know if these patients had any risk factors for mania, such as a personal or family history of bipolar disorder or other mental illness. I would like to submit that there is a risk that unexpected findings such as this do not receive enough attention amid the enthusiasm of reporting a successful new treatment (4). To avoid this, it would seem sensible from now on to carefully monitor symptoms of mania in subsequent trials, similar to advised practice in bipolar depression (5).

References

1. Cohen H, Kaplan Z, Kotler M, Kouperman I, Moisa R, Grisaru N: Repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in posttraumatic stress disorder: a double-blind, placebo-controlled study. Am J Psychiatry 2004; 161:515–524[Abstract/Free Full Text]
2. Martin JLR, Barbanoj MJ, Schlaepfer TE, Clos S, Perez V, Kulisevsky J, Gironell A: Transcranial magnetic stimulation for treating depression (Cochrane review), in The Cochrane Library, Issue 3. Chichester, UK, John Wiley & Sons, 2004
3. Nahas Z, Kozel FA, Li X, Anderson B, George MS: Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disord 2003; 5:40–47[CrossRef][Medline]
4. Cuervo LG, Clarke M: Balancing benefits and harms in health care (editorial). BMJ 2003; 327:65–66[Free Full Text]
5. Gijsman HJ, Geddes JR, Rendell JA, Nolen WA, Goodwin GM: Antidepressants for bipolar depression: a systematic review of randomised controlled trials. Am J Psychiatry 2004; 161:1537–1547[Abstract/Free Full Text]

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