David A. Kahn

Treatment of depression in women: a summary of the expert consensus guidelines.

Women constitute two-thirds of patients suffering from common depressive disorders, making the treatment of depression in women a substantial public health concern. However, high-quality, empirical data on depressive disorders specific to women are limited, and there are no comprehensive evidence-based practice guidelines on the best treatments for these illnesses. To bridge the gap between research evidence and key clinical decisions, the authors developed a survey of expert opinion concerning treatment of four depressive conditions specific to women: premenstrual dysphoric disorder, depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause. The survey asked about 858 treatment options in 117 clinical situations and included a broad range of pharmacological, psychosocial, and alternative medicine approaches. The survey was sent to 40 national experts on women’s mental health issues, 36 (90%) of whom completed it. The options, scored using a modified version of the RAND Corporation’s 9-point scale for rating appropriateness of medical decisions, were assigned one of three categorical rankings—first line/preferred choice, second line/alternate choice, third line/usually inappropriate—based on the 95% confidence interval of each item’s mean rating. The expert panel reached consensus (defined as a non-random distribution of scores by chi-square “goodness-of-fit” test) on 76% of the options, with greater consensus in situations involving severe symptoms. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. The authors summarize the expert consensus methodology they used and then, for each of the four key areas, review the treatment literature and summarize the experts’ recommendations and how they relate to the research findings. For women with severe symptoms in each area we asked about, the first-line recommendation was antidepressant medication combined with other modalities (generally psychotherapy). These recommendations parallel existing guidelines for severe depression in general populations. For initial treatment of milder symptoms in each situation, the panel was less uniform in recommending antidepressants, and either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (during conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation. In evaluating many of the treatment options, the experts had to extrapolate beyond controlled data in comparing treatment options with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women, and can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

Dissociated effects of amphetamine on arousal and cortical blood flow in humans

The effects of intravenous amphetamine infusion (0.3 mg/kg) on cerebral blood flow (CBF) and measures of autonomic and behavioral arousal were studied in 12 normal male volunteers in a placebo-controlled crossover design. Nonsignificant decreases were seen in CBF (measured by 133Xe inhalation), despite significant increases in autonomic and behavioral arousal. The apparent dissociation of CBF and arousal appears to be compatible with other human experiments suggesting that amphetamine decreases CBF and metabolism, as well as with neurobiological findings on the effects of catecholamines on resting cortical activity and mechanisms of increased attention. The results differ substantially, however, from findings of increased CBF and metabolism in animals. Although the larger doses used in animals most likely explain the discrepancy, technical limitations in human brain imaging cannot be excluded.

Medication treatment of bipolar disorder 2000: a summary of the expert consensus guidelines.

&NA; The original Expert Consensus Guidelines on the Treatment of Bipolar Disorder were published in 1996. Since that time, a variety of new treatments for bipolar disorder have been reported; however, evidence for these treatments varies widely, with data especially limited regarding comparisons between treatments and how to sequence them. For this reason, a new survey of expert opinion was undertaken to bridge gaps between the research evidence and key clinical decisions. The results of this new survey, which was completed by 58 experts, are presented in The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000, which was published in April 2000 as a Postgraduate Medicine Special Report. In this article, the authors describe the methodology used in the survey and summarize the clinical recommendations given in the resulting guidelines. The expert panel reached consensus on many key strategies, including acute and preventive treatment of mania (euphoric, mixed, and dysphoric subtypes), depression, rapid cycling, and approaches to managing treatment resistance and comorbid psychiatric conditions. Use of a mood stabilizer is recommended in all phases of treatment. Divalproex (especially for mixed or dysphoric subtypes) and lithium are the primary mood stabilizers for both acute and preventive treatment of mania. If monotherapy with these agents fails, the next recommended intervention is to combine them. This combination of lithium and divalproex can then serve as the foundation to which other medications are added if needed. Carbamazepine is the leading alternative mood stabilizer for mania. The experts rated the other new anticonvulsants as second‐line options (i.e., their use is recommended if lithium, divalproex, and carbamazepine fail or are contraindicated). For milder depression, a mood stabilizer, especially lithium, may be used as monotherapy. Divalproex and lamotrigine are other first‐line choices. For more severe depression, the experts recommend combining a standard antidepressant with lithium or divalproex. Bupropion, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine are preferred antidepressants. The antidepressants should usually be tapered 2–6 months after remission. Monotherapy with divalproex is recommended for the initial treatment of either depression or mania in rapid‐cycling bipolar disorder. Antipsychotics are recommended for use in combination with the above regimens for mania or depression with psychosis, and as potential adjuncts in nonpsychotic episodes. Atypical antipsychotics, especially olanzapine and risperidone, were generally preferred over conventional antipsychotics. The guidelines also include recommendations concerning the use of electroconvulsive therapy (ECT), clozapine, thyroid hormone, stimulants, and various novel agents for patients with treatment‐refractory bipolar illness. The experts reached high levels of consensus on key steps in treating bipolar disorder despite obvious gaps in high‐quality data. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data; however, their recommendations are generally conservative. Experts give their strongest support to initial strategies and medications for which high‐quality research data or longstanding patterns of clinical usage exist. Within the limits of expert opinion and with the understanding that new research data may take precedence, these guidelines provide clear pathways for addressing common clinical questions and can be used to inform clinicians and educate patients about the relative merits of a variety of interventions.

Gabapentin-induced delirium and dependence.

Gabapentin (Neurontin) is approved by the US Food and Drug Administration for treatment of epilepsy and post-herpetic neuralgia. Despite lack of strong evidence, gabapentin is also often prescribed off-label for psychiatric conditions. The case described here involved a 38-year-old male physician with substance intoxication delirium and psychoactive substance dependence due to high self-administered doses of gabapentin, which had been prescribed at lower doses in combination with buspirone and bupropion for depression and anxiety. This unusual case of gabapentin dependence and abuse involved toxic delirium, intense cravings, and a prolonged post-withdrawal confusional state reminiscent of ben-zodiazepine withdrawal. Gabapentin is a central nervous system inhibitory agent with likely gamma-aminobutyric acid (GABA)-ergic and non-GABAergic mechanisms of action. The similarity between benzodiazepine withdrawal and what this patient experienced with gabapentin suggests a common role for GABA-related effects. The case reported here suggests the need for heightened concern regarding the off-label prescription of this drug to vulnerable individuals with psychiatric conditions. (Journal of Psychiatric Practice 2009;15:314-319).

Memantine and catatonia: a case report and literature review.

Catatonia is a movement disorder with various possible etiologies. The majority of cases are associated with an underlying mood or psychotic disorder, while others are caused by medical conditions. Currently, benzodiazepines are the first-line psychopharmacologic agents in the treatment of catatonia. However, several cases have been reported in which treatment with memantine proved to be effective. We present the case of a 92-year-old female with major depressive disorder and associated catatonic symptoms. In this case, the patients symptoms remitted quickly after the initiation of memantine. We review the possible causes of catatonia and pharmacologic treatments for the condition and highlight the possible benefits of N-methylD-aspartic acid receptor antagonists such as memantine in the treatment of catatonia. (Journal of Psychiatric Practice 2011;17:292–299).

Bupropion and sertraline combination treatment in refractory depression

A sizeable minority of depressed patients, estimated at 15-20%, suffer chronic symptoms which often persist despite appropriate treatment. The search for new, more efficacious pharmacotherapies has included testing existing medications for additional therapeutic effects, such as in combination treatment. Four treatment- refractory patients who presented to the authors for clinical care are described, in which the combination of bupropion and sertraline was effective for a major depressive episode. None of the patients experienced adverse effects. Two carried the diagnosis of unipolar depression, and two, bipolar disorder. All had prior adequate, but ineffective, separate trials of buproprion and a selective serotonin re-uptake inhibitor (SSRI), including sertraline. All had chronic depression with multiple failed medication treatments, arguing against the alternative explanation that their improvement represented a placebo response or spontaneous remission. The efficacious combination of sertraline and bupropion may be due to synergism of its two distinct antidepressant mechanisms involving serotonergic, dopaminergic and noradrenergic systems.

Neurotoxicity with therapeutic lithium levels: a case report.

This case report describes the history and hospital course of an otherwise healthy 20-year-old male with bipolar I disorder who developed symptoms of severe lithium toxicity, culminating in a seizure, despite a level of lithium of only 0.8 mEq/L, within the usual therapeutic range. The discussion emphasizes that lithium toxicity is diagnosed by clinical symptoms and can occur even at usual therapeutic blood levels.

The Safety of Switching Rapidly from Tricyclic Antidepressants to Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors (MAOIs) are increasingly used for patients who do not respond to an initial trial of tricyclic antidepressants (TCAs). Although there are insufficient data documenting the optimal manner for switching a patient from a TCA to an MAOI, standard references advise a drug-free interval of at least 1 week. In clinical practice, however, such a delay may be difficult to observe. In order to explore the safety of a more rapid switch from TCA to MAOI therapy, we survey members of our department (Columbia University) as to their experience with different methods of switching patients from TCAs to MAOIs. Thirty-three respondents reported having switched an estimated 432 patients over the course of 3 years, with 178 patients switched within 4 days of discontinuing TCA therapy, including 63 who had the MAOI added while still being tapered from the TCA. More experienced psychiatrists tended to be less conservative, some using time intervals of 4 days or less. No adverse reactions were reported, including hypertensive and hyperpyrexic crises. This retrospective survey and an accompanying review of the literature suggest that the recommended drug-free interval of a week or more when switching patients from TCAs to MAOIs may be overly conservative.

Major depressive disorder with psychotic features may lead to misdiagnosis of dementia: a case report and review of the literature.

Major depressive disorder (MDD) with psychotic features is relatively frequent in patients with greater depressive symptom severity and is associated with a poorer course of illness and greater functional impairment than MDD without psychotic features. Multiple studies have found that patients with psychotic mood disorders demonstrate significantly poorer cognitive performance in a variety of areas than those with nonpsychotic mood disorders. The Mini Mental State Examination (MMSE) and the Dementia Rating Scale, Second Edition (DRS-2) are widely used to measure cognitive functions in research on MDD with psychotic features. Established total raw score cut-offs of 24 on the MMSE and 137 on the DRS-2 in published manuals suggest possible global cognitive impairment and dementia, respectively. Limited research is available on these suggested cut-offs for patients with MDD with psychotic features. We document the therapeutic benefit of electroconvulsive therapy (ECT), which is usually associated with short-term cognitive impairment, in a 68-year-old woman with psychotic depression whose MMSE and DRS-2 scores initially suggested possible global cognitive impairment and dementia. Over the course of four ECT treatments, the patients MMSE scores progressively increased. After the second ECT treatment, the patient no longer met criteria for global cognitive impairment. With each treatment, depression severity, measured by the 24-item Hamilton Rating Scale for Depression, improved sequentially. Thus, the suggested cut-off scores for the MMSE and the DRS-2 in patients with MDD with psychotic features may in some cases produce false-positive indications of dementia.

Effects of ect on the TRH stimulation test

The prognostic value of the TRH stimulation test was evaluated in 23 inpatients with major depressive disorder before and after a trial of ECT. In contrast to previous reports, the peak TSH response to TRH was significantly decreased after treatment compared with before treatment. This effect was consistent across individuals and subgroups (responders/nonresponders; unilateral/bilateral ECT). The particular ECT technique used in the study may account for the discrepancies between these findings and those previously reported by other authors.