Thomas L. Schwartz

Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: A naturalistic study

BACKGROUND The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. METHODS This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. RESULTS The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD(24)) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD(24) response rate was 27.2% (55/202); remission rate (HRSD(24) < or = 9) was 15.8% (32/202). Montgomery Asberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. CONCLUSIONS These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.

A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression

BACKGROUND Previous reports have described the effects of vagus nerve stimulation plus treatment as usual (VNS+TAU) during open trials of patients with treatment-resistant depression (TRD). To better understand these effects on long-term outcome, we compared 12-month VNS+TAU outcomes with those of a comparable TRD group. METHODS Admission criteria were similar for those receiving VNS+TAU (n = 205) or only TAU (n = 124). In the primary analysis, repeated-measures linear regression was used to compare the VNS+TAU group (monthly data) with the TAU group (quarterly data) according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR(30)). RESULTS The two groups had similar baseline demographic data, psychiatric and treatment histories, and degrees of treatment resistance, except that more TAU participants had at least 10 prior major depressive episodes, and the VNS+TAU group had more electroconvulsive therapy before study entry. Vagus nerve stimulation plus treatment as usual was associated with greater improvement per month in IDS-SR(30) than TAU across 12 months (p < .001). Response rates according to the 24-item Hamilton Rating Scale for Depression (last observation carried forward) at 12 months were 27% for VNS+TAU and 13% for TAU (p < .011). Both groups received similar TAU (drugs and electroconvulsive therapy) during follow-up. CONCLUSIONS This comparison of two similar but nonrandomized TRD groups showed that VNS+TAU was associated with a greater antidepressant benefit over 12 months.

Psychiatric medication‐induced obesity: a review

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the aetiology of this weight gain and the potential treatments being used to alleviate this side‐effect. We found solid evidence that weight gain is often associated with the mood stabilizers, and antipsychotics and antidepressants. Only few weight neutral or weight loss producing psychotropics are available, and weight gain, outside of an immediate side‐effect, may generate secondary side‐effects and medical comorbidity. Weight gain may cause hypertension, diabetes, osteoarthritis, sedentary lifestyle, coronary artery disease, etc. Given the likelihood of inducing weight gain with psychotropic medications and the longitudinal impact on physical health, a thorough literature review is warranted to determine the epidemiology, aetiology and treatment options of psychotropic‐induced weight gain.

Glutamate Neurocircuitry: Theoretical Underpinnings in Schizophrenia

The Dopamine Hypothesis of Schizophrenia is actively being challenged by the NMDA Receptor Hypofunctioning Hypothesis of Schizophrenia. The latter hypothesis may actually be the starting point in neuronal pathways that ultimately modifies dopamine pathways involved in generating both positive and negative symptoms of schizophrenia postulated by the former hypothesis. The authors suggest that even this latter, NMDA receptor-based, hypothesis is likely too narrow and offer a review of typical glutamate and dopamine-based neurocircuitry, propose genetic vulnerabilities impacting glutamate neurocircuitry, and provide a broad interpretation of a possible etiology of schizophrenia. In conclusion, there is a brief review of potential schizophrenia treatments that rely on the etiologic theory provided in the body of the paper.

Psychiatric medication induced obesity: an aetiologic review

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment, but consensus shows that weight gain is prominent. The present review looked at the aetiology and cause of weight gain associated with psychotropic use and presents hypotheses as to why patients gain weight on antipsychotics, mood stabilizers and antidepressants. It is found that most psychotropic medications induce some weight gain, and clinicians are encouraged to utilize active interventions to alleviate the weight gain in order to prevent more serious obesity related comorbidities.

Psychiatric medication‐induced obesity: treatment options

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. The authors undertook a comprehensive literature review in order to provide a better understanding of novel treatment options in regards to alleviating weight gained by use of antidepressants, antipsychotics, and mood stabilizers. There are no agents for management of this weight gain approved by the Food and Drug Administration (FDA), and existing studies on options are mainly uncontrolled, small‐scale projects with limited power to produce coherent conclusions. There is a clear need for larger studies on existing options, and future psychotropics without these side‐effects are currently in the pipeline.

Weight decline in patients switching from olanzapine to quetiapine

This open-label study investigated the strategy of switching patients who had gained excessive weight on olanzapine to quetiapine, with assessments of safety and continued efficacy as well as weight change. Patients who were psychiatrically stable on olanzapine but had gained >20% in weight and had body mass index >25 mg/kg(2) were switched to quetiapine over a 4-week period and followed for 6 weeks, the total study duration being 10 weeks. Assessments included weight change, antipsychotic efficacy using the Positive and Negative Symptom Syndrome Scale (PANSS), extrapyramidal adverse events using the Simpson-Angus Scale (SAS), and laboratory studies for metabolic measures. Of 16 enrolled patients, 12 completed the study. Mean weight loss was 2.25 kg (Cohens d = 0.12; P = 0.03). There were no significant changes in PANSS total scores, SAS scores, or metabolic parameters. Switching patients to quetiapine, appears to be a viable strategy for managing olanzapine-induced weight gain as indicated by this 10-week open-label study. Prospective controlled trials of longer duration and larger number of subjects are needed.

Tiagabine in anxiety disorders

GABA has been implicated in both the aetiology and treatment of anxiety. Tiagabine is currently the only selective GABA reuptake inhibitor available in US markets; it exerts its action via GAT-1 transporter blockade presynaptically, facilitating GABA neurotransmission. Preclinical studies and current human studies suggest tiagabine possesses anxiolytic properties. The anxiolytic properties of tiagabine have also been suggested in a number of case series, open-label studies and placebo-controlled studies in patients with different anxiety disorders. Throughout these studies, tiagabine has been reasonably tolerated; the most commonly reported adverse events include dizziness, headache and nausea. Tiagabine may be a useful addition to currently available drugs for anxiety; however, the data from small open-label investigations remain to be confirmed in larger controlled studies.

Genetic data supporting the NMDA glutamate receptor hypothesis for schizophrenia.

The Dopamine Hypothesis has been the leading theory used to explain the mechanism of the clinical manifestation of schizophrenia symptoms for decades. It is unclear if excess dopaminergic activity is the primary pathophysiology causing psychosis or if this dopamine excess is triggered by upstream, downstream or neurodevelopmental abnormalities. A corollary hypothesis suggests that the glutamatergic system may be involved in the pathogenesis of schizophrenia, and that dysfunction of the glutamate system may actually lead to dopamine excess. The NMDA Receptor Hypofunction Hypothesis suggests that malfunctioning NMDA receptors may be the cause for the theoretically hypofunctioning glutamate system. This paper seeks to describe and discuss the potential underlying genetic vulnerabilities of the NMDA receptor and how aberrant genes coding for this receptor may lead to schizophrenia symptoms.

Weight Gain, Obesity, and Psychotropic Prescribing

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the etiology of this weight gain and the potential treatments being used to alleviate this side effect. The authors undertook a comprehensive literature review in order to present epidemiology, etiology, and treatment options of weight gain associated with antipsychotics, mood stabilizers, and antidepressants.