Sir: Bilateral repetitive transcranial magnetic stimulation (rTMS) using high-frequency (hf-rTMS) and low-frequency (lf-rTMS) stimulation over the left and right dorsolateral prefrontal cortex (DLPFC), respectively, was theorized to enhance antidepressant outcome. 1 Although efficacy is discussed controversially, 2,3 this stimulation paradigm at least did not induce nocuous cognitive impairments. 2,4 Cases of affective side effects have been reported with use of hf-rTMS over the left DLPFC 5,6 and with use of lf-rTMS over the right DLPFC. 7 We report a 31-year-old woman experiencing a depressive episode in the course of DSM-IV bipolar I disorder who switched to mania on day 7 of a bilateral rTMS trial.Case report. Ms. A's background included a family history positive for bipolar disorder. Her disease began in 1985 with a depressive episode followed by clear-cut manic episodes in 1987 and 1992 and a second depressive episode in 1998. While an inpatient, she was assigned to rTMS treatment in a randomized, double-blind, sham-controlled, 10-day rTMS add-on trial in June 2002. 3 Each rTMS session included hf-rTMS (20 Hz, 100% motor threshold, 10 trains of 10 seconds) over the left DLPFC followed by a subsequent lf-rTMS (1 Hz, 120% motor threshold, 20 minutes) applied over the right DLPFC. On the first day of stimulation, the patient was administered 40 mg of citalopram and 10 mg of lorazepam. Prior to this trial, paroxetine had been tapered over 4 days.At baseline, Ms. A had a score of 23 on the Hamilton Rating Scale for Depression, 8 which declined to 4 at the end of treatment (day 7). This robust improvement of her depressive features reflects remission. On day 7, she developed manic symptoms, namely motor restlessness, hyper-talkativeness, grandiose ideas, and newly emerged racing thoughts. Both rTMS and antidepressant treatment were stopped immediately, and clozapine treatment (100 mg/day) was started. Within 5 days the patient's manic symptoms vanished, but she immediately cycled to another depressive episode. Citalopram treatment (40 mg/day) was restarted for a period of 4 weeks. Due to a lack of response, Ms. A was prescribed several antidepressant regimens over the next 3 months. Eventually, amitriptyline and carbamazepine showed antidepressant efficacy after 10 weeks, without signs of mania.The question arises of whether the patient's switch to mania is to be attributed to an intrinsic effect of rTMS, citalopram, 9 or both. If the switch is considered to be treatment-related, it seems reasonable to argue that the switch to mania is more closely associated with rTMS and/or add-on modalities than to citalopram alone, as the second course of citalopram treatment in our patient did not induce a manic episode. The switch might also have been associated with discontinuation of the antidepressant paroxetine, despite adequate therapy with rTMS and citalopram. 10 In addition, this brief manic episode might be seen as part of the natural course of the patient's disease. The ephemerality of the manic episode might be...
