Synchrony Between Bipolar Mood Cycles and Lunar Tidal Cycles Ended After Initiation of Light Treatment and Treatment of Hypothyroidism.

According to a recent report, mood cycles in a group of patients with rapid cycling bipolar disorder oscillated in synchrony with lunar gravimetric tides. Mood switches in a 67-year-old woman with rapid cycling bipolar II disorder on lithium maintenance treatment were assessed with a χ periodogram and a χ analysis of the mood switches in relation to the lunar tidal cycle. During a period when she was treated with nortriptyline and her thyroid-stimulating hormone levels were elevated, her mood switches had a significant (P<0.05) 29- to 30-day periodicity, and the χ analysis showed that the switches were distributed nonrandomly in relation to the spring-neap lunar tidal cycle (P<0.0001); 14 of 15 switches occurred within 2 days of the spring tides. After nortriptyline was discontinued, thyroid-stimulating hormone levels were normalized with treatment with levothyroxine, and consistent bright light treatment was started, the synchrony between mood cycles and lunar cycles disappeared, and rapid cycling eventually stopped. The possibility that lunar mood cycling is sometimes contingent on antidepressant treatment, decreased thyroid function, and certain types of light-dark cycles needs to be considered in future research on lunar tidal influences on the course of bipolar illness.

Hotel Room Suicide: Cuyahoga, Orange, Travis, and Wayne Counties.

OBJECTIVE: To compare the suicide rates of local residents registering in local hotels with the general suicide rate in that county and to compare the suicide rates of hotel guests from outside the county with the national suicide rate. METHODS: The numbers of cases of suicide in hotel rooms and the general community were tabulated for Cuyahoga County, Ohio, for calendar years 2010-2017; in Orange County, California, and Travis County, Texas, for 2010-2012; and in Wayne County, Michigan, for 1997 to March 2005. The percentage of local residents registering in local hotel rooms was estimated from various sources to stratify the suicide risk for travelers and local residents. RESULTS: The suicide rate of local residents registering in local hotels was elevated compared to the general nonhotel population in each county (range of relative risk, 15.1-37.8; P < .0001, Poisson distribution). Hotel guests from outside each county had a reduced rate of suicide compared to the national rate (range of relative risk, 0.124-0.524; P < .05, Poisson distribution). With regard to suicide method, drug overdoses accounted for a significantly greater percentage in hotel rooms than in the nonhotel population in 3 of 4 counties (range of risk ratios, 2.03-4.51, P < .01; test of proportions), with the opposite pattern for gunshot wounds (range of risk ratios, 0.27-0.50; P < .01, test of proportions). CONCLUSIONS: Although local residents register in hotels for various reasons, there appears to be a subpopulation with a purpose of avoiding rescue. Consistent with the risk-rescue rating, means of suicide with lower lethality, eg, drug overdoses, account for a greater percentage of cases in a setting with less chance of rescue. In contrast to the local use population, the sense of purpose or meaning inherent in travel could explain the decreased risk of suicide in guests from outside the county.

Transcranial magnetic stimulation in the treatment of chronic widespread pain: a randomized controlled study.

OBJECTIVE: Our objective was to assess transcranial magnetic stimulation (TMS) in the treatment of chronic widespread pain. METHODS: Nineteen participants were randomized into 2 groups: one group receiving active TMS (n = 7) and another group receiving sham stimulation (n = 11) applied to the left dorsolateral prefrontal cortex. During sham stimulation, subjects heard a sound similar to the sound heard by those receiving the active treatment and received an active electrical stimulus to the scalp. The stimulation protocol consisted of 15 sessions completed within a 4-week period. Blind assessments were done at baseline and after each 5 sessions followed by blind assessments at 1 week, 1 month, and 3 months after the last TMS sessions. The primary outcome variable was a pain measure, the Gracely Box Intensity Scale (BIRS). RESULTS: The percentage of subjects who guessed that they were receiving TMS was similar in the 2 groups. Both the TMS group and the sham group showed a statistically significant reduction in the BIRS scores from baseline during the acute phase of treatment and the follow-up phase. However, the TMS and sham groups did not differ in the change in the BIRS scores. DISCUSSION: Although some previous clinical studies and basic science studies of TMS in treating pain are promising, this study found no difference in the analgesic effect of TMS and sham stimulation. Future studies should use a sham condition that attempts to simulate the sound and sensation of the TMS stimulation. Stimulus location and other stimulus parameters should be explored in future studies.

No change in neuropsychological functioning after receiving repetitive transcranial magnetic stimulation treatment for major depression.

Early studies of transcranial magnetic stimulation (TMS) have shown no adverse effects on neuropsychological function. However, further research using higher TMS intensities as well as a greater number of TMS pulses and with larger sample sizes is needed. We studied 68 patients with major depressive disorder who were randomized to receive either 15 sessions of sham or real TMS at 110% of the estimated prefrontal cortex threshold to the left dorsolateral prefrontal cortex. Each session consisted of 32 5-second trains of 10-Hz repetitive TMS at 110% adjusted motor threshold. A total of 24,000 pulses were given. Neuropsychological function was assessed before and immediately after TMS treatment with a battery of 8 tests. Using a higher TMS intensity as well as a greater number of pulses and having a larger sample size compared with most previous studies, this study found no negative neuropsychological effects of TMS. Changes in neuropsychological function were unrelated to changes in depression.

Volitional muscle activity paired with transcranial magnetic stimulation increases corticospinal excitability.

Studies of activity-dependent stimulation in non-human primates suggest that pairing each instance of volitional muscle activity with immediate intracortical stimulation causes long-term-potentiation-like effects. This technique holds promise for clinical rehabilitation, yet few investigators have tested activity-dependent stimulation in human subjects. In addition, no one has studied activity-dependent stimulation on the cortical representation for two separate target muscles in human subjects. We hypothesized that 40 min of transcranial magnetic stimulation (TMS) triggered from ballistic muscle activity at a mean repetition rate of 1 Hz would cause greater increases in corticospinal excitability than TMS-cued muscle activity, and that these changes would be specific to the muscle of study. Ten healthy human subjects participated in 4 separate sessions in this crossover study: (1) visually cued volitional activation of the abductor pollicis brevis (APB) muscle triggering TMS (APB-Triggered TMS), (2) volitional activation of APB in response to TMS delivered from a recording of the prior APB-Triggered TMS session (TMS-Cued APB), (3) visually cued volitional activation of the extensor digitorum (ED) triggering TMS (ED-Triggered TMS), and (4) volitional activation of ED in response to TMS delivered from a recording of the prior ED-Triggered TMS session (TMS-Cued ED). Contrary to our hypothesis, we discovered evidence of increased corticospinal excitability for all conditions as measured by change in area of the motor evoked potential. We conclude that single TMS pulses paired either before or after muscle activity may increase corticospinal excitability and that further studies are needed to clarify the optimal time window for inducing neural plasticity with activity-dependent stimulation. These findings will inform the design of future activity-dependent stimulation protocols for clinical rehabilitation.

Baseline and treatment-emergent EEG biomarkers of antidepressant medication response do not predict response to repetitive transcranial magnetic stimulation.

There has been a surge of interest in biomarkers that can rapidly predict or assess response to psychiatric treatment, as the current standard practice of extended therapeutic trials is often dissatisfying to both clinicians and patients. Electroencephalographic (EEG) biomarkers in particular have been proposed as an inexpensive yet rapid way of determining whether a patient is responding to an intervention, usually before subjective mood improvement occurs. However, even the most well-reported EEG algorithms have not been subjected to independent replication, limiting their clinical generalizability. It is also unclear whether those biomarkers can generalize beyond their original study population, e.g. to patients undergoing somatic treatments for depression. We report here analysis of EEG data from the pivotal OPT-TMS study of transcranial magnetic stimulation (rTMS) for major depressive disorder. In this dataset, previously reported biomarkers of medication response showed no significant correlation with eventual response to rTMS treatment. Furthermore, EEG power in multiple bands measured at baseline and throughout the treatment course did not correlate with or predict either binary (response/nonresponse) or continuous (Hamilton Rating Scale for Depression) outcome measures. While somewhat limited by technical difficulties in data collection, these analyses are adequately powered to detect clinically relevant biomarkers. We believe this highlights a need for wider-scale independent replication of previous EEG biomarkers, both in pharmacotherapy and neuromodulation.

Transcranial magnetic stimulation in the acute treatment of major depressive disorder: clinical response in an open-label extension trial.

BACKGROUND: This report describes the results of an open-label extension study of active trans-cranial magnetic stimulation (TMS) in medication-resistant patients with major depressive disorder who did not benefit from an initial course of therapy in a previously reported 6-week, randomized controlled study of active versus sham TMS. METHOD: Patients with DSM-IV-defined major depressive disorder were actively enrolled in the study from February 2004 through September 2005 and treated with left prefrontal TMS administered 5 times per week at 10 pulses per second, at 120% of motor threshold, for a total of 3000 pulses/session. The primary outcome was the baseline to endpoint change score on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: In those patients who received sham in the preceding randomized controlled trial (N = 85), the mean reduction in MADRS scores after 6 weeks of open-label active TMS was -17.0 (95% CI = -14.0 to -19.9). Further, at 6 weeks, 36 (42.4%) of these patients achieved response on the MADRS, and 17 patients (20.0%) remitted (MADRS score < 10). For those patients who received and did not respond to active TMS in the preceding randomized controlled trial (N = 73), the mean reduction in MADRS scores was -12.5 (95% CI = -9.7 to -15.4), and response and remission rates were 26.0% and 11.0%, respectively, after 6 weeks of additional open-label TMS treatment. CONCLUSIONS: This open-label study provides further evidence that TMS is a safe and effective treatment of major depressive disorder. Furthermore, continued active TMS provided additional benefit to some patients who failed to respond to 4 weeks of treatment, suggesting that longer courses of treatment may confer additional therapeutic benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00104611.

Transcranial magnetic stimulation reduces pain in patients with major depression: a sham-controlled study.

This study evaluated the change in reported pain in patients with medication-resistant major depression receiving transcranial magnetic stimulation (TMS) compared with sham stimulation. In this study, 68 subjects with major depression were randomized to either TMS or sham stimulation. Repetitive TMS was delivered to the left dorsolateral prefrontal cortex at a frequency of 10 Hz in 5-second trains at 110% of the estimated prefrontal cortex threshold. The level of pain was assessed before, during, and after treatment using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) item for pain in the muscles, bones, and joints. Compared with sham, TMS was associated with a significant (p < 0.05) reduction in the SAFTEE pain item during the study. The reduction in pain could not be explained by the antidepressant effects.

A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) as a treatment for depression has shown statistically significant effects, but the clinical significance of these effects has been questioned. METHODS: Patients with medication-resistant depression were randomized to receive 15 sessions of active or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at 110% the estimated prefrontal cortex threshold. Each session consisted of 32 trains of 10 Hz repetitive TMS delivered in 5-second trains. The primary end point was treatment response defined as a >or=50% decrease in Hamilton Depression Rating Scale (HDRS) score at both 1 and 2 weeks following the final repetitive TMS treatment. Remission was defined as a HDRS score < 8. RESULTS: The response rate for the TMS group was 30.6% (11/35), significantly (p = .008) greater than the 6.1% (2/33) rate in the sham group. The remission rate for the TMS group was 20% (7/35), significantly (p = .033) greater than the 3% (1/33) rate in the sham group. The HDRS scores showed a significantly (p < .002) greater decrease over time in the TMS group compared with the sham group. CONCLUSIONS: Transcranial magnetic stimulation can produce statistically and clinically significant antidepressant effects in patients with medication-resistant major depression.

Comparison of clinical efficacy and side effects for bitemporal and bifrontal electrode placement in electroconvulsive therapy.

OBJECTIVES: Bifrontal (BF) placement of electrodes in electroconvulsive therapy (ECT) has become a popular alternative to bitemporal (BT) placement. This study compares the clinical efficacy, side effects, and rehospitalization rates of BT and BF electrode placement in a community hospital setting. METHODS: Charts from 76 patients receiving ECT treatments at Harborview Medical Center from 1994 to 2000 were reviewed to extract data on the characteristics of the course of ECT, clinical response, total headaches, narcotic and nonsteroidal anti-inflammatory drug doses, as well as documentation of confusion, disorientation, memory loss, and treatment emergent need for assistance with activities of daily living. RESULTS: The BT patients experienced more clinical improvement during their stay (a 7-point greater change in Psychiatric Symptom Assessment Scale score, P < 0.05) and were significantly less likely to be rehospitalized within a 1-year time frame (odds ratio = 4.9, P = <0.05), even after controlling for relevant covariates. Although the two patient groups had equal rates of headache and analgesic administration, the BT placement caused significantly more cognitive impairment. CONCLUSIONS: This study suggests that BT electrode placement offers better efficacy but modestly greater cognitive impairment than BF electrode placement.

Shorter duration of depressive episode may predict response to repetitive transcranial magnetic stimulation.

We investigated repetitive transcranial magnetic stimulation (rTMS) as a treatment for major depression. The experimental design comprised 15 medication-free subjects with major depressive disorder who were randomly assigned to receive 10 sessions of active or sham 10-Hz rTMS to the left dorsolateral prefrontal cortex at 110% motor threshold. Depression severity was measured by the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). Nonresponders to sham were allowed to receive active rTMS with the same parameters. Response to treatment was analyzed using a random regression model including episode duration and number of prior antidepressant treatments as covariates. Treatment (rTMS vs. sham) did not significantly predict changes in depression severity. Shorter duration of episode and more lifetime treatment trials significantly predicted improvements in BDI but not HDRS scores. Data from all subjects who received active rTMS (n = 14) showed that those with a depressive episode duration of shorter than 4 years had a mean HDRS decrease of 52% compared to 6% in those with an episode duration longer than 10 years. Active rTMS was well tolerated and was not associated with neuropsychological decrements when compared to sham. No significant antidepressant effects were found for 2 weeks of rTMS compared to sham. Among all subjects receiving rTMS those with a shorter duration of the current episode showed a greater response. Patients may need more than 10 treatments to obtain full benefit from rTMS. The design of future rTMS studies should consider these issues.

Is dawn simulation effective in ameliorating the difficulty awakening in seasonal affective disorder associated with hypersomnia?

BACKGROUND: Patients with winter depression, (seasonal affective disorder, SAD) frequently complain of difficulty awakening in the morning. Dawn simulation has been found effective in treating SAD, but its effect on difficulty awakening has not been assessed. METHODS: Fifty medication-free patients with SAD associated with hypersomnia were randomized to receive either 1 week of dawn simulation (250 lux) or a dim (0.2-2 lux) placebo signal. The patients assessed their level of drowsiness upon awakening during the baseline week and during the treatment week using the Stanford sleepiness scale (SSS). A psychiatrist rated difficulty awakening after the baseline week and after the treatment week. RESULTS: Dawn simulation lowered both the difficulty awakening score (P<0.05) and the SSS score (P<0.05) compared to the placebo dawn signal. LIMITATIONS: Replication is necessary. No biological markers of circadian phase were measured. CONCLUSIONS: Compared to a placebo condition, dawn simulation appears effective in decreasing both prospectively assessed morning drowsiness and retrospectively assessed difficulty awakening. The symptom of difficulty awakening is consistent with the phase delay hypothesis of SAD. Assessment of difficulty awakening could prove useful in the evaluation of SAD.

Atracurium as a Muscle Relaxant for Electroconvulsive Therapy in a Burned Patient.

We present the case of a patient with 80% total body surface area burned who presented for anesthesia and electroconvulsive therapy (ECT) 75 days after the injury. He was presumed to be sensitive to the K(+)-releasing effects of succinylcholine and therefore was given a nondepolarizing neuromuscular blocking agent, atracurium, to which he was shown to be resistant. Anesthesia for ECT on 13 occasions was without incident. Sensitivity and K(+) release secondary to succinylcholine is discussed as well as resistance to non-depolarizing neuromuscular blocking agents.