Antidepressant Effect of 58 Sessions of rTMS

Prof. Nevzat Tarhan, M.D., Oguz Tan, M.D., Adnan Coban, M.D., Semra Kaya Baripoglu, M.D., Funda Guducu, M.D., Hasan Basri Izgi, M.D., Gokben Hizli, M.D., Oznur Ates, M.D., and Huseyin Bulut, M.D.

 

Memory Center Neuropsychiatry Clinic, Istanbul, Turkey

Sir: Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective in depression in many studies. We report the case of a pregnant woman with recurrent major depressive disorder and panic disorder during her second pregnancy who received substantial benefit from 58 sessions of rTMS during pregnancy before giving birth to a healthy baby. Nineteen more sessions of rTMS were given during lactation.

Case Report

Ms. A, a 30-year old in 2007, presented with recurrent major depressive disorder and panic disorder according to DSM-IV criteria. She had no other medical problem, no personality disorder, and no psychosocial stressor and had never used substances or alcohol. There was no significant feature in her family medical history. She had had 5 episodes of major depression (in 1995, 1997, 1999, 2002, 2004). The first one in 1995 was the only episode with psychotic features, treated with antidepressant and antipsychotic drugs. Between the first and second episode, remission had not been attained; therefore, she had had to leave the university because of loss of functioning. In 1997, she had her second severe depressive episode despite the fact that she had been receiving maintenance pharmacologic treatment. By aggressive outpatient pharmacotherapy, she attained remission that lasted until 1999, by which time she had married, discontinued her antidepressant medications under the control of a psychiatrist before a planned pregnancy, became pregnant, gave birth to her first baby, and lactated. Four months after the delivery, when she had been lactating, the third episode occurred in 1999. Having discontinued the lactation, she received pharmacotherapy and psychotherapy for 4 years, during which time she was maintained in a state of partial recovery until the fourth depressive episode, in 2002. She received her first inpatient treatment and underwent 8 sessions of electroconvulsive therapy (ECT), which alleviated symptoms but did not, however, provide remission. From the age of 18 to 27 years, she received pharmaco-therapy continually except for 1.5 years (during the first pregnancy and lactation, 1998–1999), the only period in which remission had been attained. During that 9 years' course of illness, she had received monotherapy with amitriptyline 300 mg daily, sertraline 200 mg daily, and venlafaxine 600 mg daily; in addition to antidepressant medications, she had also been treated with zuclopenthixol, risperidone, olanzapine, lithium, thyroid hormone, carbamazepine, and valproic acid because of psychotic features at the first episode and the refractory nature of depression at later times. In May 2004, the fifth episode was accompanied by panic attacks. Although she received psychotherapy and pharmaco-therapy (fluoxetine 80 mg daily, clomipramine 150 mg daily, carbamazepine 400 mg daily, quetiapine 25 mg daily, and clonazepam 1.5 mg daily), she did not respond to 6 weeks' treatment and the clinical table continued to follow a very severe course. Since no classical treatment, including ECT, had been able to provide remission, in June 2004, without cessation of drugs, we began rTMS (Magstim Super Rapid magnetic stimulator; The Magstim Company Ltd., Spring Gardens, Whitland/Carmarthenshire, Wales, U.K.) over the left dorso-lateral prefrontal cortex. The intensity was 110% of the motor threshold, the frequency 25 Hz, 20 trains per session, 50 pulses per each train the duration of each train was 2 seconds followed by an interval of 28 seconds. Safety criteria reported by Wasserman¹ were exceeded because another study by our group² and our unpublished data on 178 patients (O.T., A.C., N.T., et al., 2004–2006) exceeding these criteria have produced satisfactory and safe results. Scores on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) by rTMS sessions are shown in Table 1 and Figure 1. After the 15th session, the diagnosis of pregnancy was made. Forty-seven days had passed after the menstruation. She had been strictly prohibited from getting pregnant for many years because of aggressive and continuous pharmacotherapy, and she had reported that she had been using an effective form of birth control. Before rTMS, a pregnancy test had not been administered, because only 2 weeks had passed after the last menstruation. The patient did not report the delay of the expected menstruation because she ignored it since she sometimes experienced menstruation delay. She preferred to continue pregnancy, stop medications, and receive rTMS following informed consent. She was also under close obstetric follow-up. Neither maternal nor fetal complication occurred during pregnancy. Four days after the 58th session, she gave birth to a healthy girl, at the term, in early 2005. The baby weighed 3200 g and was 49 cm tall. Complete physical and neurologic examination, screening tests for phenylketonuria and hypothyroidism, and hearing assessment of the newborn revealed no abnormalities. The newborn did not have congenital hip dysplasia, congenital cardiac disease, cleft lip, or cleft palate. There were no gastrointestinal, pulmonary, or muscular abnormalities. Twenty days later, we restarted rTMS to prevent depression relapse. She continued lactation. Ms. A responded (response defined as a 50% decrease in HAM-D-17 score) to rTMS at the end of the 50th session (6 months after beginning rTMS, with rTMS given in varying intervals). She attained remission (remission defined as a HAM-D-17 score below 8) at the end of the 68th session, approximately 1 year after beginning rTMS. No seizure or other significant side effect occurred. Although depression remitted with rTMS, since panic disorder was aggravated, the patient began treatment with fluoxetine (which was increased to 80 mg daily) once she stopped lactating 8 months after the delivery. The patient received 35 sessions of rTMS in the first trimester, 15 sessions in the second trimester, 8 sessions in the third trimester (for a total of 58 sessions during the pregnancy), and 19 sessions during 7.5 months after the delivery. Depression was still in remission 22 months after the delivery. Panic disorder, followed up with no clinical scale, decreased during pregnancy and postpartum 6 months, but then recurred. The child's physical development and neurologic development were normal through 22 months; there was no diagnosis of disease, except a viral upper respiratory infection lasting a few days. rTMS has been shown to be useful in the treatment of depression.^4–10 A pregnant woman receiving rTMS in the second trimester has been reported in another study.¹¹ Our patient received rTMS in all trimesters. Varying of intervals between rTMS sessions was due to the patient's request and also regarding the literature reporting that daily stimulation is not essential.^12–14 It seems that although rTMS is effective, a greater number of sessions or sessions of longer durations than those reported in previous studies are needed to produce significant results. On the other hand, rTMS given at intervals may be useful to improve and maintain the mood.^11,12 Furthermore, even if rTMS is not useful in the acute treatment, improvement in mood may be observed a few months later.¹² Although the fact that response and remission took nearly a year is more consistent with the natural history of depression than with a therapeutic response to rTMS, our patient's history of depression had tended to follow a chronic and recurrent course in that she had received pharmacotherapy and psychotherapy for a long time and underwent ECT without any significant recovery except during her first planned pregnancy and lactation. It may be suspected that pregnancy itself might have resulted in remission of depressive symptoms. However, contrary to clinical lore, pregnancy is not always a time of emotional well-being; pregnant and nonpregnant women have similar rates of depression.¹⁵ Furthermore, our patient's first pregnancy had not resulted in remission; on the contrary, her first pregnancy was a planned pregnancy that occurred after remission, and depression subsequently recurred during lactation. Finally, a few studies have employed rTMS in a small number of patients with panic disorder.^16,17 It seems that rTMS parameters given in depression may not prevent relapses in panic disorder.

Acknowledgments