Improvement of quality of life in panic disorder with escitalopram, citalopram, or placebo.

BACKGROUND: It has been argued that measurement of outcome in panic disorder should not be limited to monitoring the number of panic attacks, but should include all domains that affect patient quality of life. METHODS: Data from a randomized prospective comparison of escitalopram, citalopram, and placebo in patients with DSM-IV panic disorder were analyzed with regard to measurements of impairment of quality of life. The subscales of the Panic and Agoraphobia Scale (P&A) (Panic Attacks, Agoraphobic Avoidance, Anticipatory Anxiety, Functional and Social Disability, and Worries about Health) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were analyzed. RESULTS: Treatment with escitalopram was associated with significant improvement on all 5 subscales of the P&A. Citalopram was significantly different from placebo in 3 subscales. Escitalopram and citalopram were significantly better than placebo in improving quality of life (measured by the total score of the Q-LES-Q Scale). Escitalopram was superior to placebo on 12 of 16 items of the Q-LES-Q, while citalopram was superior on 7 items. CONCLUSION: The P&A scale was more robust than measurement of panic frequency in differentiating medication from placebo. Escitalopram treatment was associated with improvement on all assessed domains that impair quality of life in panic disorder. Measurement of clinical improvement should not be solely based on panic attack frequency, but should also include assessment of a broad range of domains that affect patient quality of life.

Magnetic motor threshold and response to TMS in major depressive disorder.

OBJECTIVE: The aim of this study was to examine motor threshold (MT) during treatment with transcranial magnetic stimulation (TMS). METHOD: The TMS was administered to 46 patients with depression and 13 controls. TMS was performed at 90% power of measured MT. The stimulation frequency was 10 Hz for 6 s, for 20 trains, with 30 s inter-train intervals. The trial included 20 sessions. Patients and controls were assessed on various outcome measures. RESULTS: The MT values were comparable between patients and controls. Neither demographic nor clinical variables were factors in determining MT. MT was not shown to have any predictive value regarding outcome of treatment. CONCLUSION: In this study, MT at baseline or changes in MT during the treatment period were not able to discriminate between patients and controls and were not found to have any predictive value with regard to treatment outcome.

Magnetic and seizure thresholds before and after six electroconvulsive treatments.

OBJECTIVES: Electroconvulsive therapy (ECT) is a well-established treatment in psychiatry. It has been reported that in patients with nondelusional major depression, transcranial magnetic stimulation (TMS) may substitute for ECT. To explore whether ECT and TMS share mechanisms of action, we studied the effects of ECT on both seizure threshold (ST) and magnetic motor threshold (MT). METHODS: We measured ST and MT in 10 patients referred for ECT. MT was defined as the minimal power of the TMS equipment at which a motor evoked potential (MEP) response could be detected 50% of the time. ST was defined as the minimal intensity of electrical stimulation needed to elicit an adequate seizure. ECT was performed following the methods recommended by the American Psychiatric Association. All subjects signed an informed consent for participation in the research. RESULTS: We measured MT and ST in 10 patients before and after 6 ECT treatments. No changes in MT were detected from the treatment (paired t-test: t = 1.05, SD = 4.78, p = 0.25). ST, on the other hand, increased significantly with treatment (paired t-test: t = 2.99, SD = 190.20, p < 0.001). CONCLUSIONS: ECT and TMS do not share a common mechanism at least with regard to MT and ST.

Coadministration of melatonin and fluoxetine does not improve the 3-month outcome following ECT.

At least 50% of patients with manic depressive disorder (MDD) treated successfully with electroconvulsive therapy (ECT) will experience a relapse within the first year of follow-up. Sleep disturbances are very common in MDD and may constitute forerunners of relapse. In this study we tested the hypothesis that melatonin, a sleep-promoting hormone, would decrease the 3-month relapse rate after successful ECT. We included in the study patients with MDD successfully treated with ECT (post-ECT Hamilton Rating Scale for Depression [HRSD] < or = 10). Patients were blindly randomized to two groups, one receiving fluoxetine + placebo and one receiving fluoxetine + melatonin. Assessments (HRSD, Brief Psychiatric Rating Scale, Global Assessment of Function Scale, Global Depression Scale, Pittsburgh Sleep Quality Index, Mini-Mental State Exam, and pill count) were performed for 12 weeks after ECT. Ten of the 35 patients (28.5%) relapsed during the follow-up period. Relapse rates were similar in both groups of patients. Sleep reports were not improved by melatonin. Patients who achieved a higher functional state post-ECT relapsed less often. We conclude that the addition of melatonin to on-going fluoxetine treatment did not have a beneficial effect either on the 3-month outcome post-ECT or on the sleep reports of these patients.

Transcranial magnetic stimulation-induced switch into mania: a report of two cases.

BACKGROUND: Transcranial magnetic stimulation is a novel, experimental procedure in the treatment of psychiatric disorders, most notably mood disorders. Transcranial magnetic stimulation is currently being widely studied in other applications, and its efficacies and potential side effects are being investigated. METHODS: Transcranial magnetic stimulation was administered five times a week for 4 weeks. RESULTS: In this report, a manic episode followed treatment with transcranial magnetic stimulation in two patients. CONCLUSIONS: Clinicians should be aware that, like with other antidepressive treatments, a switch into mania might complicate treatment with transcranial magnetic stimulation in bipolar patients.

Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial.

The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder (PD). Twenty-five outpatients having PD with or without agoraphobia were included. These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day. Treatment-resistant PD was defined as a less than 20% reduction in score on the Panic Self-Questionnaire (number of attacks per week) (PSQ) and the Clinical Anxiety Scale With Panic Attacks (CAS+PA). These patients continued to receive fluoxetine 20 mg/day and were randomly assigned to additionally receive either pindolol (2.5 mg three times daily) or placebo for the following 4 weeks. Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression (HAM-D), the CAS+PA, the NIMH Anxiety Scale, the PSQ, and the Clinical Global Impression Scale. The data were analyzed using a repeated-measures analysis of variance (ANOVA) and a t-test for independent samples. Patients treated with the combination of pindolol and fluoxetine (N = 13) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales, with the exception of HAM-D. The statistical differences were shown using the repeated-measures ANOVA (baseline, week 2, week 4) and also with t-tests from the second week of the trial. These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD.

The effect of electroconvulsive therapy (ECT) on implicit memory: skill learning and perceptual priming in patients with major depression.

While explicit memory in amnesics is impaired, their implicit memory remains preserved. Memory impairment is one of the side effects of electroconvulsive therapy (ECT). ECT patients are expected to show impairment on explicit but not implicit tasks. The present study examined 17 normal controls and 17 patients with severe major depressive disorder who underwent right unilateral ECT. Patients were tested in three sessions: 24-48 hours prior to, 24-48 hours following the first ECT, and 24-48 hours following the eighth ECT. The controls were tested in three sessions, at time intervals that paralleled those of the patients. Implicit memory was tested by the perceptual priming task - Partial Picture-Identification (PPI). The skill learning task used entailed solving the Tower of Hanoi puzzle (TOHP). Explicit memory was tested by picture recall from the PPI task, verbal recall of information regarding the TOHP, and by the Visual Paired Association (VPA) test. Results showed that explicit questions about the implicit tasks were impaired following ECT treatment. Patients' learning ability, as measured by the VPA task, was only impaired in the first testing session, prior to ECT treatment, reflecting the effect of depression. In addition, groups only differed in the first session on the learning rate of the skill learning task. Perceptual priming was preserved in the patients' group in all sessions, indicating that it is resilient to the effect of depression and ECT. The results are interpreted in terms of the differential effect of depression and ECT on explicit and implicit memory.

Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS), a new method for the stimulation of the central nervous system, is being proposed as a potential new treatment in patients with major depressive disorder (MDD). We tested the hypothesis that rTMS would be as effective as electroconvulsive therapy (ECT) in patients with MDD. METHODS: 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. CONCLUSIONS: Overall ECT was a more potent treatment for patients with MDD, this being particularly evident in patients with MDD and psychosis; however, in patients with MDD without psychosis the effects of rTMS were similar to those of ECT. The results we report are encouraging and support an important role for rTMS in the treatment of severe MDD; however, additional blinded studies are needed to precisely define this role.

Transcranial magnetic stimulation is effective in the treatment of relapse of depression.

INTRODUCTION: The aim of this preliminary report is to demonstrate the efficacy of rapid transcranial magnetic stimulation (rTMS) in the treatment of relapsed major depressive disorder (MDD) patients. METHODS: Four patients with major depressive disorder who were successfully treated with rTMS received a second course of rTMS treatment. Patients were evaluated with the Hamilton Depression Rating Scale - 21 items, the Brief Psychiatric Rating Scale, the Global Depression Scale and the Global Assessment Scale in both trials. The statistical analysis was performed with paired t-tests and chi squares. RESULTS: Clinical ratings demonstrated a significant improvement at the end of both trials. No significant differences were found between the ratings at the end of the treatment courses. CONCLUSION: rTMS was successfully used in the treatment of relapsed MDD patients who had previously responsed to rTMS. ( Int J Psych Clin Pract 2000; 4: 223 - 226).

Aminophylline increases seizure length during electroconvulsive therapy.

Electroconvulsive therapy (ECT) is considered to be one of the most effective treatments for patients with major depression and persistent psychosis. Seizure characteristics probably determine the therapeutic effect of ECT; as a consequence, short seizures are accepted as one of the factors of poor outcome. During most ECT courses seizure threshold increases and seizure duration decreases. Methylxanthine preparations, caffeine, and theophylline have been used to prolong seizure duration. The use of aminophylline, more readily available than caffeine, has not been well documented. The objective of this study was to test the effects of aminophylline on seizure length. Fourteen drug-free patients with diagnoses of affective disorder or psychotic episode receiving ECT participated in this study. Seizure length was assessed clinically and per EEG. Statistical comparisons were done using paired t tests. A significant increase (p < 0.04) in seizure length was achieved and maintained on three subsequent treatments with aminophylline. No adverse events were noted from the addition of aminophylline.

Chronic treatment with repetitive transcranial magnetic stimulation inhibits seizure induction by electroconvulsive shock in rats.

BACKGROUND: Studies in laboratory animals suggest that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive shock (ECS) increase seizure inhibition acutely. This study was designed to explore whether chronic rTMS would also have seizure inhibition properties. METHODS: To this purpose we administered rTMS (Magstim Rapid) and sham rTMS twice daily (2.5 T, 4-sec train duration, 20 Hz) to two groups of 10 rats for 16 days. The rTMS coil was a 50-mm figure-8 coil held directly over the rat's head. Raters were blind to experimental groups. On days 11, 17, and 21 (5 days after the last rTMS) ECS was administered with a Siemens convulsator using three electrical charge levels. Variables examined were the presence or absence of seizures and seizure length (measured from the initiation of the tonic contraction until the end of the limb movement). RESULTS: At day 11 rTMS had no effect on seizures, and both rTMS and sham rTMS animals convulsed equally. At day 17, however, rTMS-treated animals convulsed significantly less (both at presence/absence of seizures, and at seizure length) than sham rTMS animals. At day 21 the effects of rTMS had disappeared. CONCLUSIONS: These findings suggest that rTMS administered chronically leads to changes in seizure threshold similar to those reported for ECS and ECT; however, these effects were short-lived.

Melatonin for the treatment of sleep disturbances in major depressive disorder.

OBJECTIVE: The authors' goal was to examine the hypnotic effects of slow-release melatonin during the initial 4 weeks of treatment with fluoxetine in 19 patients with major depressive disorder. METHOD: Twenty-four outpatients with major depressive disorder were included in the study; 19 completed the study. Ten patients were treated with fluoxetine plus slow-release melatonin and nine were given fluoxetine plus placebo in a double-blind protocol for 4 weeks. Response was assessed by using rating scales for depression and sleep. RESULTS: The 10 patients given slow-release melatonin reported significantly better scores on the Pittsburgh Sleep Quality Index than the nine patients given placebo. No significant differences in the rate of improvement in depressive symptoms were noted between the two groups. No particular side effects were noted from the combination of fluoxetine and slow-release melatonin. CONCLUSIONS: Slow-release melatonin was effective in improving the sleep of patients with major depressive disorder. Slow-release melatonin had no effect on the rate of improvement in symptoms of major depressive disorder. The authors conclude that the role of slow-release melatonin for sleep disturbances in major depressive disorder should be investigated further.

Clozapine for the treatment of agitated-depressed patients with cognitive impairment: a report of three cases.

Clozapine, an atypical antipsychotic, is mainly approved for the treatment of resistant schizophrenia. However, a substantial body of evidence suggests that it might be useful in other psychiatric indications, such as treatment-resistant depression, Parkinson's disease, and dementia. In this report we present the cases of three patients hospitalized at the psychiatric division of the Sheba Medical Center, diagnosed with major depressive disorder with cognitive impairment, whose presenting symptom was agitation. These patients were nonresponders to various treatment modalities. However, treatment with clozapine brought about a favorable response.

[Intravenous lignocaine for chronic pain: an 18-month experience].

Intravenous injection of lignocaine relieves pain in animals with experimentally induced pain, and in man, mainly those with neuropathic pain. 106 patients were treated with intravenous lignocaine during a period of 18 months (212 treatment sessions). Blood pressure, heart rate and pain scores were continuously monitored after an intravenous bolus of lignocaine, 1 mg/kg, followed by continuous infusion of lignocaine, 5 mg/kg during 1 hour. There was significant pain relief after each session in most patients, lasting from a few hours to 4 weeks. There were no significant side effects. We present 2 of our patients. Due to its simplicity, efficacy and safety, intravenous lignocaine injection is recommended for those with neuropathic pain unrelieved by other therapeutic modalities.

Labetalol does not lengthen asystole during electroconvulsive therapy.

Labetalol, a combined alpha- and beta-adrenergic blocker is often used to attenuate the transient increases in heart rate and blood pressure that accompany electroconvulsive therapy (ECT). It has been suggested that labetalol should not be administered during ECT without the protection provided by anticholinergic medications, because of its potential severe bradycardic effects. We present our experience with 32 patients from all age groups who received labetalol without anticholinergic treatment during ECT. None of the patients demonstrated adverse bradycardic effects. We conclude that administration of labetalol during ECT does not routinely require premedication with anticholinergic drugs and does not lengthen asystole.

The treatment of comorbid premature ejaculation and panic disorder with fluoxetine.

Premature ejaculation is a common sexual disturbance among men. Both open-label and double-blind studies have demonstrated the effectiveness of serotonergic medications for this disorder. These studies support the hypothesis that the serotonergic system has an important role in the modulation of sexual response, especially attainment of orgasm. Serotonergic dysfunction also has been linked to the pathogenesis of panic disorder. Several studies have demonstrated the efficacy of serotonergic drugs in this disorder. The purpose of the present study was to examine the efficacy of fluoxetine, a serotonin selective reuptake inhibitor for the treatment of comorbid premature ejaculation and panic disorder, in 10 men in an open-label design. The patients were given 20 mg of fluoxetine for 8 weeks of the study. Parameters pertaining to sexual function and measures of anxiety were examined. Improvement of premature ejaculation was noted as of week 2 of the study, whereas measures of panic and sexual satisfaction became statistically significant only as of week 4. Further studies with larger samples and longer periods of follow-up are needed in order to determine the usefulness of fluoxetine for the treatment of comorbid premature ejaculation and panic disorder.

Personality differences between obsessive-compulsive disorder subtypes: washers versus checkers.

Personality differences between 'washer' and 'checker' subtypes of obsessive-compulsive disorder (OCD) were explored. Fifty-one OCD patients were recruited from several outpatient clinics in Central Israel. OCD was diagnosed according to DSM-III-R using the Structured Clinical Interview for DSM-III-R, and personality disorders were diagnosed using the Structured Clinical Interview for DSM-III-R Personality Disorders. Washers were much more likely to have personality disorders than checkers. Personality disorders were diagnosed in 12 of 13 washers vs. three of 11 checkers (chi 2 = 10.75, Fisher's exact test, P < 0.001, d.f. = 1, odds ratio = 32, CI = 2.8-365) and 21 of 27 patients with mixed OCD symptoms. The results support the validity of the washer-checker subdivision and might explain the relative refractoriness of washers to conventional intervention.