Antidepressant Effect of Combined Ketamine and Electroconvulsive Therapy on Patients With Major Depressive Disorder: A Randomized Trial.

BACKGROUND: One of the shortcomings of the available treatments for major depressive disorder (MDD) is the time delay between starting the treatment and achieving an antidepressant response. OBJECTIVES: We aimed to determine the effect of Ketamine as a synergistic antidepressant and anesthetic agent on MDD in electroconvulsive therapy (ECT). PATIENTS AND METHODS: Twenty-two patients with MDD received Ketamine and Propofol as anesthetic agents compared with 20 patients as the control group who received Propofol in a double-blind randomized clinical trial. The Hamilton rating scale for depression was used to determine the changes in symptoms severity during ECT and a 2-week follow-up. RESULTS: Both groups showed a reduction in depression severity, but there was no significant difference between the groups in the recovery process (P = 0.92). However, the cognitive performance recovery time in the Ketamine group was lower than that in the control group (P = 0.042). CONCLUSIONS: This study could not show the effect of Ketamine on depression recovery in a 2-week follow-up period. Nevertheless, Ketamine may provide a better cognitive performance in patients under ECT.

Granisetron as an add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study.

Some 5-HT3 antagonists such as ondansetron have shown beneficial effects on negative symptoms of patients with schizophrenia. We aimed to evaluate the efficacy of granisetron (another 5-HT3 antagonist) add-on therapy in the treatment of negative symptoms of patients with stable schizophrenia. In a randomized, double-blind, and placebo-controlled study, forty stable patients with schizophrenia (DSM-IV-TR), were randomized to either granisetron (1 mg twice daily) or placebo (twice daily) in addition to risperidone up to 6 mg/day for eight weeks. The patients were assessed using positive and negative syndrome scale (PANSS) and extrapyramidal symptom rating scale (ESRS) at baseline, week 4 and 8. Hamilton depression rating scale (HDRS) was used to assess depression at baseline and week 8. Thirty-eight patients completed the trial. Granisetron group showed a significantly greater improvement on negative subscale than the placebo group at endpoint [t(38) = 6.046, mean difference (±95% CI) = 3.2(1.8-3.7), P < 0.001]. The same effect was observed for total score [t(38) = 4.168, mean difference (95% CI) = 3.2(1.6-4.7), P < 0.001]. However the placebo and granisetron groups did not differ in their reduction of positive and general psychopathology symptoms scores. HDRS scores and its changes did not differ between the two groups. The ESRS score at week 4 was significantly lower in the granisetron than the placebo group while the two groups showed similar ESRS score at week 8. Frequency of other side effects was similar between the two groups. In summary, granisetron add-on can safely and effectively reduce the primary negative symptoms of patients with schizophrenia.

Remifentanil added to propofol for induction of anesthesia can reduce reorientation time after electroconvulsive therapy in patients with severe mania.

OBJECTIVES: To investigate the effect of adding remifentanil to propofol used in the induction of anesthesia in efficacy, and to investigate the cognitive adverse effects of electroconvulsive therapy (ECT) in the treatment of patients with severe mania. METHODS: Thirty-eight patients' condition was diagnosed as manic episode by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and were prescribed ECT by their physicians were included in a double-blind study and were randomly allocated to receive premedication with either remifentanil-atropine (study) or saline-atropine (control). Induction of anesthesia was done with propofol (1 mg/kg) and succinylcholine (0.5 mg/kg) in all patients. Assessments included seizure duration, Young Mania Rating Scale (YMRS), Mini-Mental State Examination (MMSE), and immediate cognitive adverse effects. RESULTS: Twenty-nine patients with 98 ECT sessions completed treatment. There were no differences between the 2 groups in relation to age, sex, duration of disease, weight, marital status, seizure duration, YMRS, and MMSE. However, immediate cognitive adverse effects were significantly lower in remifentanil group.

Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial.

RATIONAL: It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia. OBJECTIVE: This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial. METHODS: Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45 years. All patients were inpatients and were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion: 20 to risperidone (6 mg/day) plus sildenafil (75 mg/day) and 20 to risperidone (6 mg/day) plus placebo. The principal measure of outcome was Positive and Negative Syndrome Scale (PANSS). RESULTS: Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F = 4.77, df = 1; P = 0.03; F = 5.91, df = 1, P = 0.02 respectively). CONCLUSION: Therapy with 75 mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11).

Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania.

BACKGROUND: Considerable amount of biochemical data supports the potential involvement of protein kinase C in the pathophysiology and treatment of bipolar disorder. The aim of this double-blind, placebo-controlled study was to investigate the efficacy and tolerability of tamoxifen as an adjunct to lithium for the treatment of acute mania in hospitalized bipolar patients. METHODS: Eligible participants were 40 inpatients, between the ages of 19 and 49 years with current manic episode. Patients were randomly allocated to lithium (1-1.2 mEq/L) + tamoxifen 80 mg/day (group A) or lithium (1-1.2 mEq/L) + placebo (group B) for a 6-week, double-blind, placebo-controlled study. The principal measure of outcome was the Young Mania Rating Scale. The raters used standardized instructions for Young Mania Rating Scale. RESULTS: Young Mania Rating Scale scores improved with tamoxifen. The difference between the two protocols was significant as indicated by the effect of the group, the between-subjects factor (F=5.41, df=1, p=0.02). A significant difference was observed on the Positive and Negative Syndrome Scale total score at week 6 in the two groups. The difference between the two groups in the frequency of side effects was not significant except for fatigue that occurred more often in the tamoxifen group. LIMITATIONS: Tamoxifen is an antagonist of estrogen receptor as well. CONCLUSION: The results demonstrate that the combination of tamoxifen with lithium was superior to lithium alone for the rapid reduction of manic symptoms. The combined use of tamoxifen with lithium was well tolerated in these acutely manic patients.