Repeated Transcranial Magnetic Stimulation

A truly revolutionary new treatment for depression is repeated transcranial magnetic stimulation (rTMS). In this treatment, a magnetic paddle is held over a certain area of the front of the skull. The paddle gives off repeated and rapid magnetic pulses which gently stimulate the outer one to two inch layer of the left frontal lobe of the brain. It is painless, takes roughly 20 minutes per treatment session, doesn’t require hospitalization or anesthesia, and causes very few side-effects. In one 20 minute session, typically a total of 1600 pulses will stimulate the left frontal lobe, an area involved in depressive disorders. Research also shows that this stimulation will have indirect effects on other parts of the brain as well. Several well-designed studies show that it helps many patients resistant to medications. The research shows that it is almost as good as electro-convulsive therapy (ECT), but has many fewer side-effects and a much lower cost and ease of administration. Unfortunately, while it is much less expensive than ECT, it is more expensive than a number of low cost medications available to treat serious depressive disorders.  Also, maintenance treatments every 3 weeks are usually necessary to maintain the benefit.

While more research is necessary, rTMS may end up being a better therapy than medication for some patients due to its near absence of side-effects. Up to now, its use has been primarily limited to research centers for medication resistant patients. Usually, 10-20 daily treatment sessions are needed at a cost of $75 to $125 each (I hope to offer it, and I expect my costs will be $60, lower than anywhere else in the U.S.  Maintenance treatment of one session every three weeks is usually needed to maintain the beneficial effect. There is the possibility that two sessions a day for 5-10 days may work faster and at a lower cost, but this has not yet been researched.  In any case, rTMS would cost $100 to $300 per month for patients needing maintenance therapy to avoid medication depending on the facility's charges plus a monthly office visit.  While this is more than generic medications, it is about the same most patented medications.  

Perhaps more often, patients will use medications to try to maintain their improvement without maintenance rTMS, although I personally favor avoiding medication whenever possible.  Since maintenance medications do help avoid relapses in some ECT patients, the same will probably be found true for rTMS patients. For medication resistant patients, the somewhat higher cost of rTMS might be more than offset by being able to avoid psychiatric hospitalizations and medication side-effects.

Because of its higher cost, most patients may choose medication therapy first and use rTMS as a back-up therapy.  rTMS has already been approved by the FDA, but not specifically for depression.  Thus, like many medications, it can and already is being used "off-label." Unfortunately, rTMS will probably not be available from most treatment programs until after an FDA approved treatment trial for major depressive disorder.  A phase II trial is currently underway and should be completed by 2005. Only a very few private practice psychiatrists in the U.S. are using it at the present time. The cost of the equipment is quite high, over $30,000.

rTMS Helped Depression in Chinese Study: In a 2-week DB, sham-controlled study of add-on rTMS for 30 medication-resistant patients with DSM-IV major depressive disorder or bipolar disorder, 10 sessions of active rTMS at either faster (20 Hz) or slower (5 Hz) at 100% motor threshold demonstrated a superior reduction of depression severity compared to sham stimulation (active = 56% vs. sham = 16%). No difference in clinical response was observed between 5 Hz and 20 Hz active rTMS. Add-On rTMS for Medication-Resistant Depression: A Randomized, Double-Blind, Sham-Controlled Trial in Chinese Patients. Su TP, et al. National Yang-Ming University, Taipei, Taiwan. J Clin Psychiatry. 2005 Jul;66(7):930-937.

rTMS Again as Good as ECT for Depression with Improved Memory and Thinking Instead of Deteriorated: In a randomized study of 30 patients with treatment-refractory non-psychotic major depression, an average of ten treatments with either unilateral ECT or left prefrontal rTMS (repeated Transcranial Magnetic Stimulation) were given. Treatment response was 46% for ECT and 44% for rTMS showing a reduction of 50% or more in HAM-D depression scores. In patients treated with rTMS, cognitive performance remained constant or improved and memory complaints became fewer, whereas in the ECT group memory recall deficits appeared and memory complaints remained. Distinctive neurocognitive effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy in major depression. Schulze-Rauschenbach SC, et al. University of Bonn, Germany. Br J Psychiatry. 2005 May;186:410-6. 

Transcranial Magnetic Stimulation: A University of Iowa DB study of depressed post-stroke patients who had not improved on anti-depressants had the anti-depressant stopped. Then, patients received 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham (placebo) treatment. HAM-D depression scores decreased with treatment and there were no more reported "side-effects" with treatment than with placebo. Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study. Jorge RE, Robinson RG, Tateno A, Narushima K, Acion L, Moser D, Arndt S, Chemerinski E. Biol Psychiatry. 2004 Feb 15;55(4):398-405. 

Longer Treatment May be Necessary: 2 weeks (i.e., 10 rTMS treatments) may be insufficient to obtain substantive clinical improvement. Fitzgerald et al reported a 20%–25% reduction in depressive symptoms after 10 rTMS treatments, whereas after 20 treatments most subjects experienced a 50%–60% reduction in depressive symptoms. Fitzgerald PB, Brown TL, et al. Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry 2003;60:1002-8.

Meta-Analysis Says rTMS Works: A meta-analysis of 12 studies with 230 adults of all treatments were between 5 and 10 days over the left DLPFC found a moderate effect size of 0.53 with a mean HAM-D change after rTMS of 7.24 in the activetreatment group and 3.58 in the sham-treatment group. J Psychiatr Pract 2002;8:270-275. 

rTMS Slow Frequency Helped in DB: In a DB PC study, researchers have announces in a letter that results support the therapeutic potential of rTMS in the low-frequency range of 1 Hz on right prefrontal cortex for the treatment of refractory major depression. Slow right prefrontal transcranial magnetic stimulation as a treatment for medication-resistant depression: a double-blind, placebo-controlled study. Kauffmann CD, Cheema MA, Miller BE. Depress Anxiety. 2004;19(1):59-62

rTMS Either Left or Right Found Beneficial: Archives of General Psychiatry 10/03, Paul B. Fitzgerald,  Monash University in Melbourne, Australia. In sham-controlled trial, 60 patients with multiple antidepressant-resistant depressions were separated into three similar groups. They received 20 five-second High Frequency Left TMS (HFL-TMS) trains at 10 Hz, five 60-second Low Frequency Right TMS (LFR-TMS) trains at 1 Hz, or sham stimulation. On the MADRS Depression Scale, each group did much better than the sham (P < .005 for all) but there was no difference between the two treatments. Psychomotor agitation at baseline predicted successful treatment response. Repetitive TMS was generally well tolerated, and no major adverse events were reported.

TMS Seizure Therapy Said Better than ECT: First study of using TMS to intentionally cause a seizure while patient under anesthesia reports that it works as well as ECT with fewer side-effects. Magnetic Seizure Therapy Improves Mood in Refractory Major Depression. Kosel M, Frick C, Lisanby SH, Fisch HU, Schlaepfer TE. Univ Bern. Neuropsychopharmacology. 2003 Aug 27

rTMS Case Anxious Depr in Preg: Repetitive transcranial magnetic stimulation with an eletromagnet on the scalp has promise in treating Parkinson’s disease, cortical epilepsy and depression. DB studies, all positive=Am J Psychiatry 154:1752-6 ‘97, Lancet 348:233-7 ‘96, Neuroreport 6:1853-6 ’96. rTMS minimal risk of seizure and no fetal exposure to anesthetics as with ECT or psychotropic meds. Ziad Nahas, J Clin Psychiatry 1/99, 60:50-2. ECT can induce premature labor in about 1% of cases.

rTMS Didn't Add to SSRI Antidepressant Benefit: In a double blind controlled study, rTMS results in a similar antidepressant effect to sham in combination with paroxetine. Both groups had the same delay in improvement. rTMS seems not to be efficient as an add-on treatment to pharmacological medication in non-resistant major depression. Repetitive transcranial magnetic stimulation does not potentiate antidepressant treatment. Poulet E, Brunelin J, Boeuve C, Lerond J, D'Amato T, Dalery J, Saoud M. Universite Claude Bernard Lyon, France. Eur Psychiatry. 2004 Sep;19(6):382-3

Transcranial Prefrontal Magnetic Stimulation More Effective on Right: In depression TPMS more effective on left. 16 pt DB study for mania with 10 days of 20 2 second trains per day. Grisaru, Ben Gurion U, Am J Psychiatry 11/98;155:1608

rTMS in Normal Volunteers: GEORGE MS. WASSERMANN EM. WILLIAMS WA. STEPPEL J. PASCUAL-LEONE A. BASSER P. HALLETT M. POST RM. (1996) J Neuropsychiatry & Clinical Neurosciences. 8(2):172-80 rTMS in volunteers replicated a previous finding that Left pre-frontal rTMS lowered (self rated) mood, and Right pre-frontal rTMS decreased sadness.

rTMS As Good As ECT: 20 severe major depr pts randomized and did equally well with both groups showing marked improvement. Dannon, Israel, APA 5/30/98 Toronto.

rTMS No Cognitive Dysfunction: 5 depr pts Rx which causes direct subconvulsive stimulation over cortical brain regions implicated in depression. No change in mental status scores. Safe and well tolerated. Speer, NIMH, APA 5/30/98 Toronto.

rTMS helped Rx Resistant: Open trial of 14 pt with 10 daily rx with 50% much improved and 25% maintaining improvement at 4 wk f/u. Yvonne Greene, Emory, APA 5/99

rTMS Case of Psychosis: During rTMS treatment, the patient developed recurrent severe delusions, which he had never experienced before. Psychotic symptoms remitted quickly with neuroleptic medication.Conclusions: In light of preclinical findings showing increased dopaminergic activity after rTMS treatment, occurrence of psychotic symptoms should be considered a potential side effect of rTMS treatment. Biol Psychiatry 2002 Apr 1;51(7):602-3

rTMS Helps in Pilot Study: GEORGE MS. WASSERMANN EM. WILLIAMS WA. CALLAHAN A. KETTER TA. BASSER P. HALLETT M. POST RM. (1995) Neuroreport. 6(14):1853-6 Oct 2. The authors report a pilot study of such treatment in six highly medication-resistant depressed inpatients. Depression scores significantly improved for the group as a whole. This involved Left prefrontal rTMS.

rTMS Called Very Safe: PURI BK and LEWIS SW (1996) The British Journal of Psychiatry. 169, 675-677. The history behind stimulating human tissue with magnetism is summarised. TMS is painless, the currents induced in the brain are associated with energy levels perhaps a million times less than with ECT, and suggested to represent only 0.1% of the BMR of the brain itself. Seemingly, even metallic clips in the head pose no significant problem? TMS has been used diagnostically in a patient with 'presumed hysterical paraplegia' showing normal motor electrophysiology. Repetitive TMS (rTMS) may provide an alternative to ECT and work is ongoing with some good results in depression

Slow Frequency Used: MENKESA DL, BODNARC P, BALLESTEROSB RA, SWENSONA MR (1999) The J Neurol Neurosurg Psychiatry 1999;67:113-115 This paper makes a distinction between fast (FF r-TMS -stimulates cortex) and slow (SF r-TMS -inhibits cortical activity) frequency rTMS. Left frontat FF r-TMS appears to attenuate depression. This study looked at SF r-TMS to the right frontal lobe. 8 sessions of SR r-TMS were given right frontally over 6 weeks - at motor threshold. The Beck and Hamilton (Depression) scales both improved. No change occurred in controls suggesting an antidpressive effect with right frontal SF r-TMS.

rTMS Almost Equals ECT: Authors say 3 small trials vs placebo showed benefit before 2000. They compared ECT to rTMS and found equal % of recovery for patients with major depression and failing one course of meds, but that the amount of improvement slightly favored ECT (45% vs 69% BDI, 55% vs. 66% Hamilton). Pridmore S, Bruno R, Turnier-Shea Y, Reid P, Rybak M. Int J Neuropsychopharmacol 2000 Jun; 3(2):129-134

rTMS Helps Parkinson’s with Depression in Open Trial: Ten depressed patients with PD (four with major depression and six with dysthymia) received daily sessions of rTMS (frequency, 0.5 Hz; pulse duration, 0.1 msec; field intensity, 10% above the motor threshold) over both prefrontal regions (a total of 100 stimuli per prefrontal region daily) over 10 consecutive days. This treatment resulted in a moderate but significant decrease in scores of the Hamilton Depression Rating Scale (33-37%) and the Beck Depression Inventory (24-34%), which persisted 20 days after finishing the stimulation. In parallel, we observed mild improvement (18-20%) of motor symptoms. Mov Disord 2002 May;17(3):528-32

rTMS Prolongs Anti-Depressant Effect of Partial Sleep Deprivation: Using a controlled, balanced parallel design we studied, whether repetitive transcranial magnetic stimulation (rTMS) applied in the morning after PSD is able to prevent this relapse. 20 PSD responders were randomly assigned to receive either active or sham stimulation during the following 4 days after PSD. Active stimulation prolonged significantly (p < 0.001) the antidepressant effect of PSD up to 4 days. This finding indicates that rTMS is an efficacious method to prevent relapse after PSD. Life Sci 2002 Mar 1;70(15):1741-9.

rTMS Improves Cognitive Functioning in Severe Depression: 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test-B). Neurology 2002 Apr 23;58(8):1288-90. U Iowa,

rTMS Relapse as Low as ECT: major depressive disorder with or without psychotic features referred for ECT were randomly assigned to receive either ECT or rTMS. Forty-one patients who responded to either treatment constituted the sample. Patients were followed on a monthly basis and outcomes were determined with the Hamilton Rating Scale for Depression-17 items (HRSD) and the Global Assessment of Functioning (GAF) scales. Medications were routinely prescribed. RESULTS: There were no differences in the 6-month relapse rate between the groups. Overall, 20% of the patients relapsed (four from the ECT group and four from the rTMS group). Patients reported equally low and not significantly different scores in the HRSD (ECT group 8.4 +/- 5.6 and TMS group 7.9 +/- 7.1) and the GAF (ECT group 72.8 +/- 12 and TMS group 77.8 +/- 17.1) at the 6-month follow up. CONCLUSIONS: Patients treated with rTMS do as well as those treated with ECT at the 3- and 6-month follow-up points. These data suggest that the clinical gains obtained with rTMS last at least as long as those obtained with ECT. Biol Psychiatry 2002 Apr 15;51(8):687-90. Dannon, Israel.

rTMS as Good as ECT: 25 major depression (unipolar or bipolar) deemed clinically appropriate for ECT were randomly assigned to rTMS (10-20 treatments, 10 Hz, 110% motor threshold applied to the left dorsolateral prefrontal cortex for a total of 10,000-20,000 stimulations) or a course of bitemporal ECT (4-12 treatments). The primary outcome measure was the 24-item Hamilton Depression Rating Scale (HDRS). The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMS), and Clinical Global Impression scale (CGI) were secondary measures. Minimal rescue medications were utilized. RESULTS: Mean percent improvement on the baseline HDRS score did not significantly differ between the two treatments (i.e., 55% for the rTMS group vs. 64% for the ECT group [p = ns]). With response defined as a 50% reduction from baseline and a final score < or = 8 on the HDRS, there was also no significant difference between the two groups. No differences between groups on the secondary measures. U Chic, PG Janicak, Biol Psychiatry 2002 Apr 15;51(8):659-67.

rTMS Little Impact on Normals: Nineteen healthy volunteers received randomised left or right prefrontal rTMS at a frequency of 1 Hz and 100% of motor threshold in two sessions two weeks apart. RESULTS: There were significant improvements with TMS for performance in the digit symbol substitution and verbal fluency tests, but no change of mood on a number of measures. There was also a reduction of pulse rate after TMS. The only side-specific TMS-effect was on mean arterial pressure, which decreased pressure after left, but not after right prefrontal TMS. U Edinburg, BMC Psychiatry 2002;2(1):1

rTMS No Adverse Effects on Cognition: 18 depressed patients participated in a randomized double-blind cross-over study exploring the antidepressant effects of 2 weeks (10 daily) of sham, 1 Hz, or 20 Hz rTMS administered over the left dorsolateral prefrontal cortex at 100% of motor threshold (MT). A subgroup completed a battery of cognitive tests at baseline and following each 2-week phase of treatment, and differences in performance were assessed using paired t -tests and were correlated with the degree of clinical improvement using Hamilton Depression Rating Scale scores. RESULTS: There were no major changes in cognitive test scores as a result of 10 days of either 1 Hz or 20 Hz rTMS. Moreover, any minor attenuations in cognition were not related to the degree of clinical improvement. CONCLUSIONS: Cognitive functioning in many domains following 2 weeks of 1 Hz or 20 Hz rTMS at 100% MT over the left dorsolateral prefrontal cortex in depressed patients is not disrupted. J ECT 2001 Dec;17(4):259-63, NIMH, A Speers,

rTMS Review Postive: Seven controlled trials of rTMS depression were identified. Five of these were suitable for meta-analysis and show a beneficial effect of rTMS compared to placebo, with a number needed to treat of 2-3 with a 95 % confidence interval 1.6 to 4.0, total; 81 patients. Cambridge. B McNamara, Psychol Med 2001 Oct;31(7):1141-6

ECT Helps Some rTMS Resistant Patients: Seventeen patients with severe MDD who had not responded to a course of rTMS were switched to receive ECT treatments. All the patients were assessed with the Hamilton Rating Scale for Depression, the Global Assessment Functioning Scale, the Global Depression Scale, and the Pittsburgh Sleep Quality Index. Response to the treatment was defined as a 50% decrease in HDRS final score and a final GAS higher than 60. Seven out of 17 patients responded to ECT. Three out of 5 non-psychotics and 4 out of 12 psychotic patients responded. ECT seems to be an effective treatment for 40% of patients who failed to respond to rTMS treatment. Int J Neuropsychopharmacol 2001 Sep;4(3):265-8.

rTMS Helps ECT Nonreponder: Nervenarzt 2001 Sep;72(9):734-8. Pt with delusional depression not responding to five courses of ECT (61 treatments) responded quickly to rTMS. Germany, Nervenarzt 2001 Sep;72(9):734-8

rTMS Not Add to SSRI Effect: Twenty eight patients who had not yet received medication for the present depressive episode (n=12) or had failed a single trial of an antidepressant medication (n=16) were started on sertraline and randomised to receive either real of sham HF-rTMS. HF-rTMS was applied to the left dorsolateral prefrontal area in daily sessions (30 trains of 2 s, 20-40 s intertrain interval, at 90% motor threshold) on 10 consecutive working days. The results suggest that in this patient population, HF-rTMS does not add efficacy over the use of standard antidepressant medication. Spain, J Neurol Neurosurg Psychiatry 2001 Oct;71(4):546-8

rTMS Not Helpful in Elderly: 20 depressed, treatment-refractory patients (mean age 60.7 +/- 9.8 years) given five sessions of rTMS at 20 Hz for 2 seconds over 20 trains at 80% of motor threshold or identical placebo stimulation, after patients had been withdrawn from their antidepressants. There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days' follow-up. There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders (p = .03). These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS. U Iowa, Manes, Int Psychogeriatr 2001 Jun;13(2):225-31

rTMS Increases TSH & Helps Depression: double-blind conditions et al 14 medication-free subjects with major depression received individual sessions of either active or sham rTMS. rTMS was administered over the left prefrontal cortex at 10 Hz et al 100% of motor threshold, 20 trains over 10 min. Immediately before and after rTMS sessions, subjects' mood was rated with the Profile of Mood States (POMS) and the 6-Item Hamilton Depression Scale, and blood was drawn for later analysis of TSH. Subjects and raters were blind to treatment assignment. RESULTS: The group receiving active stimulation manifested significantly greater improvement on the POMS subscale of Depression (p < or = .0055) and a trend toward greater improvement on the modified Hamilton Rating (.05 < p < or =.1). No hypomania was induced. The change in TSH from pre- to post-rTMS was significantly different between active and sham sessions. U Penn, Szuba, Biol Psychiatry 2001 Jul 1;50(1):22-7

rTMS Useful tho ECT Better: 32 patients suffering major depressive episode (MDE) who had failed to respond to at least one course of medication. There was no limit to the number of treatment sessions which could be given and treatment was continued until remission occurred or response plateaued. A significant main effect for treatment type was found [Pillai trace = 0.248, F(3,28) = 3.076, p = 0.044; power = 0.656], reflecting an advantage for ECT patients on measures of depression overall, however, rTMS produced comparable results on a number of measures. Blind raters using the 17-item Hamilton Depression Rating Scale (HDRS) found the rate of remission (HDRS = ? 8) was the same (68.8%), and the percentage improvement over the course of treatment of 55.6% (rTMS) and 66.4% (ECT), while favouring ECT, was not significantly different. Significant differences were shown (p & 0.03) in percentage improvement on Beck Depression Inventory ratings (rTMS, 45.5%; ECT, 69.1%), but not for improvement in Visual Analogue ratings of mood (rTMS 42.3%; ECT, 57%). rTMS has antidepressant effects of useful proportions. Pridmore, Int J Neuropsychopharmacol 2000 Jun;3(2):129-134

rTMS Better Than Sham: PASCUAL-LEONE A. RUBIO B. PALLARDO F. CATALA MD.(1996) Lancet. 348(9022):233-7 Focal rTMS on psychotic depression. 17 medication resistance depressed patients in a randomised placebo cross-over using sham rTMS and other cortical areas. Left dorsolateral prefrontal cortex rTMS resulted in a significant decrease in scores on the Hamilton and Beck depression scales.

rTMS Better Than Sham: Twelve patients diagnosed with major depression (DSM-IV) were randomized in a sham-controlled cross-over treatment protocol of 4 weeks' duration consisting of two periods of 5 days with rTMS separated by 9 days of no stimulation. rTMS (10 Hz) was applied to the left dorsolateral prefrontal cortex. Hemodynamic changes in the prefrontal cortex during mental work were evaluated by multi-site near-infrared spectroscopy (NIRS). Scores on the Hamilton Depression Rating Scale (HAMD) decreased significantly by -5.4 points after 5 days of active stimulation, whereas it did not change (+1.6 points) after sham stimulation. Psychiatry Res 2000 Oct 30;99(3):161-72

rTMS Better Than Sham in Rx Resistant: Depressed subjects, who had failed to respond to a median of four treatment trials, were assigned in a randomized double-blind manner to receive either active (n = 10; 20 2-sec trains of 20 Hz stimulation with 58-sec intervals; delivered at 80% motor threshold with the figure-of-eight coil positioned over the left dorsolateral prefrontal cortex) or sham (n = 10; similar conditions with the coil elevated and angled 45 degrees tangentially to the scalp) rTMS. These sequences were applied during 10 consecutive weekdays. Continuous electroencephalogram sampling and daily motor threshold determinations were also obtained. RESULTS: The group mean 25-item Hamilton Depression Rating Scale (HDRS) score was 37.2 (+/- 2.0 SEM) points. Adjusted mean decreases in HDRS scores were 14.0 (+/- 3.7) and 0.2 (+/- 4.1) points for the active and control groups, respectively (p <.05). One of 10 subjects receiving active treatment demonstrated a robust response (i.e., HDRS decreased from 47 to 7 points); three other patients demonstrated 40-45% decreases in HDRS scores. No patients receiving sham treatment demonstrated partial or full responses. CONCLUSIONS: A 2-week course of active rTMS resulted in statistically significant but clinically modest reductions of depressive symptoms. RM Berman, Yale, Biol Psychiatry 2000 Feb 15;47(4):332-7

rTMS = ECT for Non-Psychotic, ECT > for Psychotic: Forty patients with MDD referred for ECT were randomly assigned to either ECT or rTMS. Repetitive transcranial magnetic stimulation was performed at 90% power of the motor threshold. The stimulation frequency was 10 Hz for either 2 sec (first eight patients) or 6 sec (final 12 patients) for 20 trains. Patients were treated for up to 20 treatment days. Electroconvulsive therapy was performed according to standard protocols. RESULTS: Overall patients responded best to ECT (chi(2) = 3.8, p <.05). Patients with MDD and psychosis responded significantly better to ECT (chi(2) = 9.2, p <. 01), whereas MDD patients without psychosis responded similarly to both treatments (chi(2) = 0.0, ns). The analysis of variance with repeated measures of clinical variables for the whole sample revealed significant treatment effects for both groups; however, interaction between group and treatment was seen only for the Global Assessment of Function and the Sleep assessment. When the psychosis-nonpsychosis grouping was considered, patients with psychosis responded dramatically better to ECT in all assessments, whereas those without psychosis responded similarly to both treatments. Israel, Grunhaus, Biol Psychiatry 2000 Feb 15;47(4):314-24

rTMS 5 Days Not Benefit Drug Refractory: double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. Padberg, Munich, Psychiatry Res 1999 Nov 29;88(3):163-71

rTMS No Better than Sham for Two Weeks: groups (9 each) receiving real and sham rTMS improved in mood significantly over the 2-week double-blind period, but there was no significant difference between groups. CONCLUSIONS: Repetitive transcranial magnetic stimulation did not provide significantly greater improvement than did sham treatment. A 4-week course of rTMS, as administered in this study, was safe. Am J Psychiatry 1999 Jun;156(6):946-8

rTMS Appears Very Safe: Previous rTMS studies as a treatment for depression consisted of delivering 800 to 3,000 magnetic pulses per day, with 8000 to 30,000 magnetic pulses over 2 to 3 weeks. As part of a study to examine rTMS effects in sleep deprivation, healthy men were given 12,960 magnetic pulses a day for up to 3 days in 1 week of 38,880 magnetic pulses, the largest exposures of TMS to date. Despite this intense treatment regimen, there were significant side effects. Doses of up to 12,960 pulses per day appear safe and tolerable in healthy young men. Tolerability and safety of high daily doses of repetitive transcranial magnetic stimulation in healthy young men. Anderson B, et al. Medical University of South Carolina, Charleston. . J ECT 2006 Mar;22(1):49-53. Ed: The hope is that such treatment could help depression more rapidly and at a lower cost.