Robert B. Ostroff

Urinary free-cortisol levels in posttraumatic stress disorder patients.

Urinary free-cortisol levels (micrograms per day) were measured by radioimmunoassay at 2-week intervals during the course of hospitalization in the following patient groups: posttraumatic stress disorder (PTSD); major depressive disorder; bipolar I, manic; paranoid schizophrenia; and undifferentiated schizophrenia. The mean cortisol level during hospitalization was significantly lower in PTSD (33.3 ± 3.2) than in major depressive disorder (49.6 ± 5.9), bipolar I, manic (62.7 ± 6.7), and undifferentiated schizophrenia (50.1 ± 8.9), but was similar to that in paranoid schizophrenia (37.5 ± 3.9). The same differences across groups are evident in the first sample following hospital admission. This finding of low, stable cortisol levels in PTSD patients is especially noteworthy, first because of the overt signs of anxiety and depression, which would usually be expected to accompany cortisol elevations, and second because of the concomitant chronic increase in sympathetic nervous system activity shown in prior psychophysiological studies of PTSD and reflected in marked and sustained urinary catecholamine elevations previously reported in our own PTSD sample. The findings suggest a possible role of defensive organization as a basis for the low, constricted cortisol levels in PTSD and paranoid schizophrenic patients. The data also suggest the possible usefulness of hormonal criteria as an adjunct to the clinical diagnosis of PTSD.

Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder

Urinary norepinephrine and epinephrine levels (microgram/day) were measured at two-week intervals during the course of hospitalization in the following patient groups: post-traumatic stress disorder (PTSD); major depressive disorder (MDD); bipolar I, manic (BP); paranoid schizophrenia (PS); and undifferentiated schizophrenia (US). The mean norepinephrine level during hospitalization was significantly higher in PTSD (76 +/- 10.4 micrograms/day) than in BP (60.6 +/- 8.4 micrograms/day), MDD (41.2 +/- 4.7 micrograms/day), PS (33.4 +/- 4.9 micrograms/day) and US (34.3 +/- 5.9 micrograms/day) groups, according to Duncans multiple range test, (F(4,39) = 6.94, p less than 0.0003). The norepinephrine elevations in the PTSD group were sustained throughout hospitalization. The only other group to show mean levels in this range was the BP group in the first sample after hospital admission. This finding supports prior psychophysiological studies indicating increased sympathetic nervous system activity in PTSD patients. The mean epinephrine level during hospitalization was also significantly higher in PTSD (22.7 +/- 2.4 micrograms/day) than in MDD (13.6 +/- 1.7 micrograms/day), PS (14.7 +/- 2.4 micrograms/day), and US (18.9 +/- 1.8 micrograms/day), but not higher than in BP (21.5 +/- 2.7 micrograms/day). The relationship of epinephrine levels among diagnostic groups was sustained throughout hospitalization. It appears likely that the main underlying mechanisms for elevations of both hormones are psychological, but further work will be required to establish the exact nature of these mechanisms.

Rapid antidepressant effect of ketamine in the electroconvulsive therapy setting.

Objectives Studies now provide strong evidence that the N-methyl-D-aspartate receptor antagonist ketamine possesses rapidly acting antidepressant properties. This study aimed to determine if a low dose of ketamine could be used to expedite and augment the antidepressant effects of electroconvulsive therapy (ECT) treatments in patients experiencing a severe depressive episode. Materials and Methods Subjects with major depressive disorder or bipolar disorder referred for ECT treatment of a major depressive episode were randomized to receive thiopental alone or thiopental plus ketamine (0.5 mg/kg) for anesthesia before each ECT session. The Hamilton Depression Rating Scale (HDRS) was administered at baseline and at 24 to 72 hours after the first and sixth ECT sessions. Results Electroconvulsive therapy exerted a significant antidepressant effect in both groups (F2,24 = 14.35, P < 0.001). However, there was no significant group effect or group-by-time interaction on HDRS scores. In addition, post hoc analyses of the time effect on HDRS showed no significant HDRS reduction after the first ECT session for either group. Conclusions The results of this pilot study suggest that ketamine, at a dose of 0.5 mg/kg, given just before ECT, did not enhance the antidepressant effect of ECT. Interestingly, the results further suggest that the coadministration of ketamine with a barbiturate anesthetic and ECT may attenuate the immediate antidepressant effects of the N-methyl-D-aspartate antagonist.

Imaging Onset and Propagation of ECT‐induced Seizures

Summary:  Purpose: Regions of seizure onset and propagation in human generalized tonic–clonic seizures are not well understood. Cerebral blood flow (CBF) measurements with single photon emission computed tomography (SPECT) during electroconvulsive therapy (ECT)‐induced seizures provide a unique opportunity to investigate seizure onset and propagation under controlled conditions.

Targeted prefrontal cortical activation with bifrontal ECT.

The anatomical brain regions involved in the therapeutic and adverse actions of electroconvulsive therapy (ECT) are unknown. Previous studies suggest that bifrontal vs. bitemporal ECT differ in therapeutic efficacy and cognitive side effects. We therefore performed cerebral blood flow (CBF) imaging during bitemporal vs. bifrontal ECT-induced seizures to identify regions crucial for the differences between these treatments. Patients with major depression, undergoing bitemporal or bifrontal ECT, were studied. Ictal-interictal SPECT images were analyzed with statistical parametric mapping for bitemporal (n=11 image pairs in 8 patients) and bifrontal (n=4 image pairs in 2 patients) ECT-induced seizures to identify regions of ictal CBF changes. Bifrontal ECT was found to cause increases in CBF in prefrontal and anterior cingulate regions. Bitemporal ECT, however, caused CBF increases in the lateral frontal cortex and in the anterior temporal lobes. In bifrontal ECT, a greater increase in prefrontal activation, while sparing the temporal lobes, may result in a better therapeutic response and fewer adverse effects on memory than bitemporal ECT.

The use of electroconvulsive therapy in postpartum affective disorders.

Postpartum affective disorders continue to be a major health issue for women. There is a general belief that electroconvulsive therapy (ECT) is effective in treating severe or treatment-refractory postpartum affective illnesses, but evidence to support this assertion is lacking. In this case series, we present 5 cases of women with postpartum depression and psychosis, all of whom had failed prior pharmacological therapy. All 5 women had a significant response within 3 to 6 treatments with ECT. Our findings suggest that ECT is overall an effective treatment of postpartum illnesses. In addition to being an excellent choice for women who have failed prior medication trials, ECT may also be considered for women whose severity of illness necessitates rapid symptom resolution.

Efficacy of Electroconvulsive Therapy in the Treatment of Nondepressed Psychiatric Illness in Elderly Patients: A Review of the Literature

Electroconvulsive therapy (ECT) is well established as a safe and effective treatment for several psychiatric disorders. Responsiveness to ECT does not abate with age, and data indicate that the use of ECT in the treatment of psychiatric disorders in the elderly persons has increased in recent decades. Special consideration must be given to the baseline cognitive abilities of an elderly patient prior to treatment with ECT. Much of the literature on the use of ECT in the elderly persons has focused on the treatment of mood disorders, whereas less research has been devoted to its use in the treatment of other psychiatric conditions. Although depressive syndromes remain the most common indication for ECT in the elderly persons, clinicians treating elderly patients should remain aware of the safety and efficacy of this treatment modality with other psychiatric disorders. This review examines the literature on the use of ECT in elderly patients with some common neuropsychiatric disorders including catatonia, bipolar mania, schizophrenia, dementia with behavioral disturbance, and Parkinsons disease.

Combined use of lamotrigine and electroconvulsive therapy in bipolar depression: a case series.

Objective: Lamotrigine and electroconvulsive therapy (ECT) are both safe and effective treatments for bipolar depression. Concerns exist that anticonvulsants may interfere with seizure expression during ECT or may exacerbate cognitive side effects, potentially affecting clinical response. This report examines the clinical use of concurrent ECT and lamotrigine for acute bipolar depression and the transition to maintenance therapy. Methods: Nine patients with acute bipolar depression were simultaneously treated with a course of ECT while titrating lamotrigine for maintenance therapy. We compared mean stimulus intensity, mean seizure duration, and mean time to orientation after treatment for each patient during treatment with their highest and lowest lamotrigine dose. Results: All 9 patients were treated to remission. From the lowest daily dose to the highest daily dose, mean increase in lamotrigine was 102.8 mg. Clinically adequate seizures were obtained in each patient. Lamotrigine had minimal effect on each measured ECT parameter. The interval between ECT treatments was spaced to a mean of 15.2 days. The treatment combination was well tolerated, with no serious adverse events, no rashes, and no worsening of cognitive side effects. Conclusions: Concurrent use of lamotrigine with ECT in bipolar depression seems safe, did not interfere with routine ECT practice, and allowed for transition to maintenance pharmacotherapy.

Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression

Introduction: Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivates the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamines antidepressant effects. Methods: Patients who were pursuing ketamine infusion therapy for treatment-resistant depression were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol. Results: Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first 2 weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine nonresponders did not appear to benefit from CBT. Conclusions: CBT may sustain the antidepressant effects of ketamine in treatment-resistant depression. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamines antidepressant effects.

The Use of Ketamine for the Treatment of Depression in the Context of Psychotic Symptoms: To the Editor.

Mounting evidence from a series of small clinical trials and case series suggests ketamine can have rapid and robust antidepressant (1) and possibly antisuicidal effects (2) in patients who did not respond to standard treatment options. However, because of the variable psychotomimetic effects of ketamine in healthy volunteers and exacerbation of previously experienced positive symptoms in schizophrenic volunteers (3,4), patients previously experiencing psychotic features have been excluded from the reported studies and trials. We have used ketamine as an antidepressant on several occasions in patients with severe treatment-resistant major depressive episodes with good results. Recently, after seriously considering the risks and benefits of providing off-label ketamine treatment (.5 mg/kg continuous intravenous infusion over 40 min) based on this knowledge, we treated two patients with psychotic features complicating severe depressive episodes. To our knowledge, this is the first report describing the use of ketamine as treatment in patients with a history of psychosis. The first patient was a 52-year-old woman with a long history of unipolar depression with psychotic features who presented with depressive symptoms, auditory hallucinations, paranoid delusions, and reporting a suicide plan to drink antifreeze. Current medications were venlafaxine 300 mg, ziprasidone 80 mg, clonazepam 1 mg, and zolpidem 10 mg. Ketamine infusion was chosen as the therapeutic agent because of lack of response to these medications as well as to numerous other antidepressant drugs. During infusion, the patient reported mild dissociative symptoms, fatigue, and a mild headache. After infusion, the patient denied feelings of depression. In addition to the dramatic mood improvement, her auditory hallucinations and paranoia ceased within hours of the ketamine infusion. Three ketamine infusions were performed before transitioning the patient from venlafaxine to a monoamine oxidase inhibitor as pharmacologic therapy to prevent relapse. Hamilton Depression Rating Scale scores changed from 19 to 9 over the course of the treatment. The second patient was a 55-year-old woman with a long and severe psychiatric history of schizoaffective disorder who presented with depressive symptoms and severe suicidal ideation of driving a car off the road or overdosing on pills. The patient was withdrawn, whispering, catatonic, and responding to internal stimuli. Current medications were clozapine 225 mg, lamotrigine 250 mg, and lithium 300 mg. Past history included self-mutilation, medication overdoses, and a violent psychotic episode in which she set her home on fire in response to command hallucinations. Because of severity of past depressive episodes and the fact that she had previously received ketamine as the anesthetic agent with electroconvulsive therapy with a robust antidepressant effect to the treatment even though no seizure was induced (5), ketamine infusion was administered. After infusion, her mood