Samir Kumar Praharaj

Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study.

OBJECTIVE To study the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral pre-frontal cortex (DLPFC) in patients with alcohol dependence. METHODS We performed a prospective, single-blind, sham-controlled study involving 45 patients with alcohol dependence syndrome (according to ICD-10 DCR), with Clinical Institute of Withdrawal Assessment in Alcohol Withdrawal (CIWA-Ar) scores <or=10. Patients were allocated to active and sham rTMS in a 2 : 1 ratio, such that 30 patients received active and 15 patients sham rTMS to the right DLPFC (10 Hz frequency, 4.9 seconds per train, inter-train interval of 30 seconds, 20 trains per session, total 10 sessions). The Alcohol Craving Questionnaire (ACQ-NOW) was administered to measure the severity of alcohol craving at baseline, after the last rTMS session and after 1 month of the last rTMS session. RESULTS Two-way repeated-measures analysis of variance (ANOVA) showed significant reduction in the post-rTMS ACQ-NOW total score and factor scores in the group allocated active rTMS compared to the sham stimulation. The effect size for treatment with time interaction was moderate (eta(2) = 0.401). CONCLUSIONS Right dorsolateral pre-frontal high-frequency rTMS was found to have significant anticraving effects in alcohol dependence. The results highlight the potential of rTMS which, combined with other anticraving drugs, can act as an effective strategy in reducing craving and subsequent relapse in alcohol dependence.

Clozapine-induced sialorrhea: pathophysiology and management strategies

RationaleClozapine is an atypical antipsychotic agent with proven efficacy in refractory schizophrenia, but its widespread use is limited by adverse effects such as agranulocytosis, seizures, sedation, weight gain, and sialorrhea. Clozapine-induced sialorrhea (CIS) is bothersome and has socially stigmatizing adverse effects, which result in poor treatment compliance. The pathophysiology of this condition is poorly understood and the treatment options available are based mostly on case reports and open-label studies.ObjectiveTo review the available studies on CIS.MethodAll relevant studies available through PUBMED search supplemented with manual search were undertaken.ResultThe clinical features, complications, assessment, pathophysiology, and management of CIS are discussed.ConclusionAlthough the studies evaluating the therapeutic options has limitations and no drug has been found to be superior, judicious use of pharmacological agents along with behavioral methods will reduce this troublesome side effect and enhance compliance.

Adjunctive high-frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) was not effective in obsessive–compulsive disorder but improved secondary depression

BACKGROUND There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful in obsessive-compulsive disorder (OCD) patients. METHODS Our objective was to examine efficacy of adjunctive right prefrontal high-frequency (rapid) rTMS treatment in OCD patients. 42 patients with OCD were randomly assigned to 10 sessions of add-on high-frequency right prefrontal active rTMS (10Hz, 110% of motor threshold, 4s per train, 20 trains per session) or sham stimulation. They were rated on Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A) and Clinical Global Impression-Severity of Illness (CGI-S) at baseline, day 14 and day 28. The dose of antiobsessive drug was kept constant throughout the period of assessment. RESULTS For YBOCS scores, repeated measures ANOVA showed significant main effect of treatment, but no effect of treatment over time (Pillais Trace F=1.39, p=.262). However, significant effect of treatment over time as shown by interaction effect for both HAM-D (Pillais Trace F=3.67, p=.035, eta(2)=.158) and HAM-A scores (Pillais Trace F=5.22, p=.01, eta(2)=.211) were seen. CONCLUSION Adjunctive high-frequency right prefrontal rTMS does not have any significant effect in the treatment of OCD. However, it is modestly effective in the treatment of comorbid depressive symptoms in patients with OCD.

Metformin for olanzapine‐induced weight gain: a systematic review and meta‐analysis

Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain. Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Of these, four studies (n= 105) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index (BMI). Weighted mean difference (WMD) for body weight was 5.02 (95% CI 3.93, 6.10) kg lower with metformin as compared with placebo at 12 weeks. For waist circumference, the test for heterogeneity was significant (P= 0.00002, I(2) = 85.1%). Therefore, a random effects model was used to calculate WMD, which was 1.42 (95% CI 0.29, 3.13) cm lower with metformin as compared with placebo at 12 weeks. For BMI, WMD was 1.82 (95% CI 1.44, 2.19) kg m(-2) lower with metformin as compared with placebo at 12 weeks. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain.

Efficacy of high frequency (rapid) suprathreshold repetitive transcranial magnetic stimulation of right prefrontal cortex in bipolar mania: A randomized sham controlled study

OBJECTIVE To examine the efficacy of adjunctive right prefrontal high-frequency suprathreshold rTMS treatment in bipolar affective disorder, mania patients as compared to sham stimulation. METHOD 41 right handed bipolar mania patients were randomized to receive daily sessions of active or sham rTMS (20 Hz, 110% of MT, 20 trains, 10 s intertrain interval) over the right dorsolateral prefrontal cortex for 10 days. Mania was rated using Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI) at baseline, and after 5th and 10th rTMS. RESULT For YMRS scores, repeated measures ANOVA showed a significant effect of treatment over time as shown by interaction effect (F=12.95, df=1.51/58.94, p<0.001, Greenhouse-Geisser corrected). For CGI-S, repeated measures ANOVA showed a significant interaction effect of treatment over time (F=5.34, df=1.36/53.01, p=0.016, Greenhouse-Geisser corrected). CONCLUSION High-frequency supra-threshold right prefrontal rTMS in bipolar, mania patients was well tolerated and found to be effective as add-on to standard pharmacotherapy.

Slow wave sleep deficits as a trait marker in patients with schizophrenia

BACKGROUND Among the sleep abnormalities found in schizophrenia, slow wave sleep deficits have been found to persist even after the resolution of active psychotic symptoms. Further, such abnormalities are observed in young healthy individuals at high risk of schizophrenia, which suggest that slow wave sleep deficits might be trait marker in schizophrenia. METHODS Sleep EEG was recorded in 20 right handed patients aged 18-45 years with ICD-10 DCR diagnosis of schizophrenia, 14 first degree relatives and 20 age and sex matched controls. Patients were rated on Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) for assessment of psychopathology. RESULTS There was significant difference between the three groups in total sleep period (p<.01), total sleep time (p<.01), stage shifts (p<.05), stage 1 percentage of total sleep time (p<.05), stage 2 duration (p<.05), stage 3 latency (p<.05), stage 4 duration (p<.01) and stage 4 percentage of total sleep time (p<.01). There was significant positive correlation of REM percentage of total sleep time with BPRS total score (r(s) = .488, p = .029) and PANSS positive score (r(s) = .583, p = .007), whereas significant negative correlation of REM latency was found with BPRS total score (r(s) = -.640, p = .002) and PANSS positive score (r(s) = -.657, p = .002) in the patients. CONCLUSIONS Slow wave sleep deficits are a possible trait marker in patients with schizophrenia, which needs replication in further studies.

Comparison of Anticraving Efficacy of Right and Left Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized Double-Blind Study

The objective of this study was to compare the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right versus left dorsolateral prefrontal cortex (DLPFC) in patients with alcohol dependence. Twenty patients with alcohol dependence syndrome were randomly allocated to receive either right or left rTMS over the right DLPFC (10 sessions at 10 Hz frequency; 20 trains per session; 4.9 seconds per train and intertrain interval 30 seconds) and were assessed on the Alcohol Craving Questionnaire (ACQ-NOW) to measure craving. Two-way repeated-measures analysis of variance for ACQ-NOW total score showed no main effect of group (F[1,18] = 0.0001 but significant main effect of time (F[1,18] = 185.91, p<0.0001, η(2) = 0.912). The interaction effect between group and time was not significant. There was significant reduction in craving scores in patients receiving either right or left rTMS with large effect size. However, there was no difference in anticraving efficacy between the two groups.

Efficacy of adjunctive high frequency repetitive transcranial magnetic stimulation of left prefrontal cortex in depression: a randomized sham controlled study.

OBJECTIVE To examine the efficacy of adjunctive left prefrontal high-frequency rTMS treatment in depression patients as compared to sham stimulation. METHOD 45 right handed moderate to severe depression patients according to ICD-10 DCR criteria were randomized to receive daily sessions of active or sham rTMS (10Hz, 90% of resting MT, 20 trains, 6s duration, 1200 pulses/day) over the right dorsolateral prefrontal cortex for 10 days. Depression and psychosis was rated using Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) and Brief Psychiatric Rating Scale (BPRS) respectively before and after rTMS. RESULT For SIGH-D scores, repeated measures ANOVA showed a significant effect of treatment over time as shown by interaction effect (Pillais Trace F [1/38] = 56.75, p<.001, η(2) = .60). For BPRS, repeated measures ANOVA showed a significant interaction effect of treatment over time (Pillais Trace F [1/38] = 39.87, p<.001, η(2) = .51). In psychotic depression patients, repeated measures ANOVA showed a significant effect of treatment over time for SIGH-D scores (Pillais Trace F [1/25] = 43.04, p<.001, η(2) = .63) and BPRS scores (Pillais Trace F [1/25] = 42.17, p<.001, η(2) = .63). CONCLUSION High-frequency left prefrontal rTMS was well tolerated and found to be effective as add-on to standard pharmacotherapy in nonpsychotic as well as psychotic depression.

Inhalant abuse (typewriter correction fluid) in street children.

Background:Inhalant abuse is a growing concern in India among street children. Aim:To describe the sociodemographic and clinical characteristics of 9 street children and adolescents with typewriter correction fluid abuse. Method:Nine street children who presented to the psychiatry department of Dr. Ram Manohar Lohia Hospital, New Delhi for treatment of inhalant abuse were interviewed. Findings:The inhalant abusers were boys of 10 to 17 years, school dropouts who had run away from villages of Bihar and Uttar Pradesh. In two-third of children there was domestic violence and conflict in their family, along with physical abuse by family members; in one-third it was due to alcoholic fathers. They used to “huff” typewriter correction fluid, and abused other substances as well. Conclusion:There is a need to systematically study inhalant abuse in the street children in India.

Improving tolerability of lithium with a once-daily dosing schedule.

Lithium has been proved to be highly efficacious in the treatment of bipolar affective disorder, though a narrow therapeutic index and a high incidence of troublesome side effects often leads to poor compliance in patients. Therefore, there is a need to explore treatment strategies to improve the efficacy and side effect profile of lithium. We compared the efficacy and side effect profile of a once-daily versus twice-daily dosing schedule of lithium in mania. Eighty-three manic patients according to International Classification of Diseases, 10th Revision, Diagnostic Criteria for Research, giving informed consent were randomly allocated to receive regular lithium carbonate once daily or twice daily. They were assessed using Bech-Rafaelsen Mania Rating Scale, a lithium side effect scale, hemogram, renal function test, lipid profile, and a thyroid function test at baseline and Day 7, Day 21, and Day 42. Repeated-measures analysis of variance for Bech-Rafaelsen Mania Rating Scale scores showed a significant main effect, but interaction of treatment groups over time was not significant. Those subjects receiving twice-daily lithium experienced significantly higher urinary frequency on Day 21 (P = 0.008) and Day 42 (P = 0.035). They also required significantly higher total daily dose of lithium (P = 0.017) and had lower serum lithium levels (P < 0.001). There was a significant positive correlation between urinary frequency at Day 42 with lithium dose. A twice-daily dose of lithium was of similar efficacy as the once-daily schedule but produces higher renal adverse effects that may be dose-related. Therefore, a single daily dose of lithium can be a viable method to reduce the side effects of lithium, which may lead to better patient compliance.