A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities.

BACKGROUND: Controversy persists about the use of right unilateral (RUL) and bilateral (BL) electroconvulsive therapy (ECT). While RUL ECT results in less severe short-term and long-term cognitive effects, there is concern that it is less efficacious than BL ECT. METHODS: In a double-blind study, 80 depressed patients were randomized to RULECT, with electrical dosages 50%, 150%, or 500% above the seizure threshold, or BL ECT, with an electrical dosage 150% above the threshold. Depression severity and cognitive functioning were assessed before, during, immediately after, and 2 months after ECT. Compared with baseline, responders had at least a 60% reduction in symptom scores 1 week after ECT, and were monitored for relapse for 1 year. RESULTS: High-dosage RUL and BL ECT were equivalent in response rate (65%) and approximately twice as effective as low-dosage (35%) or moderate-dosage (30%) unilateral ECT. During the week after the randomized phase, BL ECT resulted in greater impairment than any dosage of unilateral ECT in several measures of anterograde and retrograde memory. Two months after ECT, retrograde amnestic deficits were greatest among patients treated with BL ECT. Thirty-three (53%) of the 62 patients who responded to ECT relapsed, without treatment group differences. The relapse rate was greater in patients who had not responded to adequate pharmacotherapy prior to ECT and who had more severe depressive symptoms after ECT. CONCLUSION: Right unilateral ECT at high dosage is as effective as a robust form of BL ECT, but produces less severe and persistent cognitive effects.

Prolactin response to electroconvulsive therapy: effects of electrode placement and stimulus dosage.

BACKGROUND: It is unclear whether the serum prolactin (PRL) surge following electroconvulsive therapy (ECT) is a marker of optimal ECT administration. We investigated the relations among PRL surge, stimulus parameters, and outcome in major depressive disorder (MDD). METHODS: Seventy-nine patients with MDD were randomized in a double-blind trial to right unilateral (RUL) or bilateral (BL), and to low-dose (just above seizure threshold) or high-dose (2.5 x threshold) ECT. RESULTS: Change in PRL (delta PRL) varied among treatment groups, with significant effects of electrode placement (BL > RUL, p < .006), electrical dosage (high > low, p < .04), and gender (female > male, p < .005). There was no evidence that clinical improvement was associated with greater PRL surge. CONCLUSIONS: Although delta PRL varied with parameters impacting on response rates, these data indicate the PRL surge cannot serve as a useful index of clinically effective treatment. This finding does not support the view that diencephalic seizure propagation is necessary for ECT to exert therapeutic effects.

Effects of electroconvulsive therapy on plasma vasopressin and oxytocin.

BACKGROUND: Animal studies suggest that vasopressin has cognitive-enhancing properties and oxytocin may have amnestic effects. A clinical report suggests that the acute increase in oxytocin-associated neurophysin predicts clinical response to electroconvulsive therapy (ECT) in depressed patients. METHODS: Medication-free patients with major depression were randomized to receive right unilateral or bilateral ECT administered with electrical stimulus intensity at either just above seizure threshold or at 150% above seizure threshold. The associations between plasma vasopressin, oxytocin, ECT treatment parameters, clinical outcome, and cognitive effects were assessed. RESULTS: The sample comprised 55 patients. At the second ECT, patients receiving ECT at 150% above initial seizure threshold had significantly greater increases in plasma vasopressin than patients receiving low-dose ECT (ps < .01-.04), with no effects of electrode placement. At the second and ninth ECT treatments, the vasopressin or oxytocin surges were not associated with clinical improvement, seizure duration, time to orientation, or memory test performance. There were inverse trend-level associations between the acute surge in oxytocin levels at the ninth ECT and clinical response, contradicting a report in the literature. CONCLUSIONS: Overall, these findings do not support the hypothesis that diencephalic seizure propagation is central to the mechanism of action of ECT.

Naloxone in the prevention of the adverse cognitive effects of ECT: a within-subject, placebo controlled study.

Electroconvulsive therapy (ECT) is a highly effective treatment for major depression, but is also associated with characteristic cognitive side effects. Several reports document that endogenous opioids and their receptors are activated by electroconvulsive shock (ECS) and that naloxone in doses sufficient to block endogenous opioid receptors may reverse ECS-induced retrograde amnesia. This placebo-controlled, randomized, within-patient study was conducted to examine the potential of naloxone, given in doses sufficient to block opioid receptors (high dose), to ameliorate acute anterograde and retrograde memory impairments following ECT. Compared to placebo and low dose naloxone, high dose naloxone administered immediately before ECT resulted in significant reductions in anterograde amnesia, and better performance on an attention task. Both low and high dose naloxone improved verbal fluency. There were no beneficial effects of high dose naloxone on retrograde amnesia, and an indication that high dose naloxone may have worsened retrograde amnesia for shape stimuli. There were no effects of high dose naloxone on seizure duration, vital signs, and subjective side effects. The study is consistent with prior research in which change in behavioral and physiological measures was produced principally by naloxone doses sufficient to block endogenous opioid receptors and offers evidence of the potential for ameliorating some adverse cognitive effects associated with ECT.

Fluoxetine treatment of dysthymia in the elderly.

BACKGROUND: Despite their prevalence, little is known about the treatment of mild depressive syndromes in older patients. The purpose of this study was to evaluate the efficacy of fluoxetine in dysthymic disorder in the elderly. METHOD: Twenty-three elderly outpatients with dysthymic disorder (DSM-III-R criteria) entered a 13-week study of fluoxetine (2-week placebo run-in period and 11 weeks of fluoxetine treatment with a dose range of 20-60 mg/day). Ratings to assess clinical response included the Hamilton Rating Scale for Depression (HAM-D), the Clinic Global Impression (CGI), and the Cornell Dysthymia Rating Scale (CDRS). RESULTS: Nine patients (39%) had never received psychiatric treatment during the index episode, despite a long duration of illness (mean +/- SD = 18.5 +/- 17.1 years). Twenty of the 23 patients completed the entire study. The mean +/- SD HAM-D (24-item) score decreased from 14.6 +/- 3.7 to 7.9 +/- 5.0 during the trial, and the CDRS score decreased from 28.1 +/- 9.1 to 15.7 +/- 10.0. When response criteria of a 50% reduction from baseline in the HAM-D score, final HAM-D score < or = 8, and a CGI score of 1 or 2 (very much or much improved) were used, 12 (60%) of the completers were responders. Side effects were uncommon, and the fluoxetine was generally well tolerated. CONCLUSION: These preliminary findings suggest that fluoxetine is an effective treatment in elderly patients with dysthymic disorder. Double-blind, placebo-controlled studies are warranted.

Subjective side effects during electroconvulsive therapy.

In 92 depressed patients who were randomized to unilateral or bilateral electroconvulsive therapy (ECT) at either low dosage (just above seizure threshold) or high dosage (2.5 times the seizure threshold), subjective side effects were assessed with the Columbia ECT Subjective Side Effects Schedule. A research nurse administered the instrument 4 h after each treatment during the ECT course. In 41 patients, the instrument was also administered before the ECT course. Headache, disorientation, and memory complaints were the most common subjective side effects during the ECT course. Somatic side effects did not change from early to late in the ECT course, and were not influenced by ECT electrode placement or dosage. Most individual somatic side effects, including nausea, tiredness, and muscle aches/pains did not change from pre-ECT to during the ECT course, and may have been a function of the persistent somatic symptoms of depression. Cognitive complaints increased from pre-ECT to during the ECT course, but there was no overall change from pre-ECT to immediately after the ECT course. Cognitive complaints were greater with bilateral compared with unilateral ECT, with no significant effect of electrical dosage. During the ECT course, subjective mood improved and psychomotor agitation decreased, particularly in clinical responders. These findings suggest that most putative somatic side effects are related to the depressive state rather than being induced by ECT. The observed changes reinforce the need to evaluate both subjective and objective side effects during ECT.

Effects of electroconvulsive therapy on plasma GABA.

There are no published data on the effects of seizures on indices of gamma-aminobutyric acid (GABA) function in human subjects. In study 1, the effects of electroconvulsive therapy (ECT) on free plasma GABA were studied in 39 inpatients with major depressive disorder. Acutely after ECT, free plasma GABA was significantly reduced for up to 1 h after seizure termination, and this finding replicated strongly in a subgroup of six patients who received a second course of ECT. In a second study at a different site that compared sham ECT and real ECT in seven patients, some doubt was raised about the replicability of the acute effect of ECT on GABA levels. Nonetheless, the strength of the findings in the larger study 1 sample suggests that, unlike virtually all other biochemical indices, free plasma GABA may be reduced acutely after ECT. This acute decrease could reflect decreased levels of GABA in brain extracellular space or decreased brain turnover. In study 1, compared with ECT nonresponders, ECT responders had higher GABA levels at both baseline and after a course of ECT. Because plasma GABA levels are known to be low in a subset of patients with major depression, the higher GABA levels observed in clinical responders before and after the ECT course indirectly suggest that patients least abnormal in GABA levels may show superior clinical response. This also suggests that low plasma GABA is not a state marker for depression.

Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy.

BACKGROUND: The efficacy of electroconvulsive therapy in major depression is established, but the importance of the electrical dosage and electrode placement in relation to efficacy and side effects is uncertain. METHODS: In a double-blind study, we randomly assigned 96 depressed patients to receive right unilateral or bilateral electroconvulsive therapy at either a low electrical dose (just above the seizure threshold) or a high dose (2.5 times the threshold). Symptoms of depression and cognitive functioning were assessed before, during, immediately after, and two months after therapy. Patients who responded to treatment were followed for one year to assess the rate of relapse. RESULTS: The response rate for low-dose unilateral electroconvulsive therapy was 17 percent, as compared with 43 percent for high-dose unilateral therapy (P = 0.054), 65 percent for low-dose bilateral therapy (P = 0.001), and 63 percent for high-dose bilateral therapy (P = 0.001). Regardless of electrode placement, high dosage resulted in more rapid improvement (P < 0.05). Compared with the low-dose unilateral group, the high-dose unilateral group took 83 percent longer (P < 0.001) to recover orientation after seizure induction, whereas the combined bilateral groups took 252 percent longer (P < 0.001). During the week after treatment, there was three times more retrograde amnesia about personal information with bilateral therapy (P < 0.001). There were no differences between treatment groups in cognitive effects two months after treatment. Forty-one of the 70 patients who responded to therapy (59 percent) relapsed, and there were no differences between treatment groups. CONCLUSIONS: Increasing the electrical dosage increases the efficacy of right unilateral electroconvulsive therapy, although not to the level of bilateral therapy. High electrical dosage is associated with a more rapid response, and unilateral treatment is associated with less severe cognitive side effects after treatment.

Personality disorders in elderly patients with dysthymic disorder.

The authors evaluated personality disorders in elderly patients with DSM-IV dysthymic disorder (DD) to identify prevalent personality disorders and their clinical correlates. Outpatients (>/=60 years; N=76) with DD were evaluated; most were male (65.8%) and had late age at onset (>50 years: 60.5%). Axis II disorders were present in 31.2% of patients, with obsessive-compulsive personality disorder (OCD; 17.1%) and avoidant personality disorder (11.8%) being the most common. Personality disorders were associated with an earlier age at onset of depressive illness, greater lifetime history of comorbid Axis I disorders, greater severity of depressive symptoms, and lower socioeconomic status. Personality disorders occurred in a minority of elderly patients with DD and mainly comprised the obsessive-compulsive and avoidant subtypes, similar to reports of personality disorders in elderly patients with major depression. In contrast, young adults with DD have been shown consistently to have personality disorders at high frequency. Together with the predominance of late onset and the lack of psychiatric comorbidity, the current findings on personality disorders reinforce our view that DD in elderly patients is typically a different disorder from DD in young adults.