Sakina J. Rizvi

Deep Brain Stimulation for Treatment-Resistant Depression: Follow-Up After 3 to 6 Years

OBJECTIVE A prevalence of at least 30% for treatment-resistant depression has prompted the investigation of alternative treatment strategies. Deep brain stimulation (DBS) is a promising targeted approach involving the bilateral placement of electrodes at specific neuroanatomical sites. Given the invasive and experimental nature of DBS for treatment-resistant depression, it is important to obtain both short-term and long-term effectiveness and safety data. This report represents an extended follow-up of 20 patients with treatment-resistant depression who received DBS to the subcallosal cingulate gyrus (Brodmanns area 25). METHOD After an initial 12-month study of DBS, patients were seen annually and at a last follow-up visit to assess depression severity, functional outcomes, and adverse events. RESULTS The average response rates 1, 2, and 3 years after DBS implantation were 62.5%, 46.2%, and 75%, respectively. At the last follow-up visit (range=3-6 years), the average response rate was 64.3%. Functional impairment in the areas of physical health and social functioning progressively improved up to the last follow-up visit. No significant adverse events were reported during this follow-up, although two patients died by suicide during depressive relapses. CONCLUSIONS These data suggest that in the long term, DBS remains a safe and effective treatment for treatment-resistant depression. Additional trials with larger samples are needed to confirm these findings.

A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression.

OBJECT Deep brain stimulation (DBS) has been recently investigated as a treatment for major depression. One of the proposed targets for this application is the subcallosal cingulate gyrus (SCG). To date, promising results after SCG DBS have been reported by a single center. In the present study the authors investigated whether these findings may be replicated at different institutions. They conducted a 3-center prospective open-label trial of SCG DBS for 12 months in patients with treatment-resistant depression. METHODS Twenty-one patients underwent implantation of bilateral SCG electrodes. The authors examined the reduction in Hamilton Rating Scale for Depression (HRSD-17) score from baseline (RESP50). RESULTS Patients treated with SCG DBS had an RESP50 of 57% at 1 month, 48% at 6 months, and 29% at 12 months. The response rate after 12 months of DBS, however, increased to 62% when defined as a reduction in the baseline HRSD-17 of 40% or more. Reductions in depressive symptomatology were associated with amelioration in disease severity in patients who responded to surgery. CONCLUSIONS Overall, findings from this study corroborate the results of previous reports showing that outcome of SCG DBS may be replicated across centers.

Sexual Dysfunction, Depression, and the Impact of Antidepressants

Sexual dysfunction is a common symptom of depression. Although decreased libido is most often reported, difficulties with arousal, resulting in vaginal dryness in women and erectile dysfunction in men, and absent or delayed orgasm are also prevalent. Sexual dysfunction is also a frequent adverse effect of treatment with most antidepressants and is one of the predominant reasons for premature drug discontinuation. Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants and have significant effects on arousal and orgasm compared with antidepressants that target norepinephrine, dopamine, and melatonin systems. The availability of an antidepressant that does not cause or exacerbate sexual dysfunction represents an advance in pharmacotherapy for mood disorders and should reduce treatment noncompliance and decrease the need for switching antidepressants or adding antidotes. The purpose of this review was to provide an update on the prevalence, psychobiology, and relative adverse effect burden of sexual dysfunction associated with different antidepressants.

A Double-Blind Comparison of Sexual Functioning, Antidepressant Efficacy, and Tolerability Between Agomelatine and Venlafaxine XR

Impaired sexual function is associated with major depressive disorder in the untreated state and is often more prevalent during antidepressant therapy, which frequently results in poor treatment compliance. In this double-blind, multicenter study, the effects of agomelatine (an MT1 and MT2 agonist and 5HT-2C antagonist) and venlafaxine XR on sexual function were compared using the Sex Effects Scale in depressed patients. A total of 276 male and female patients received either agomelatine (50 mg) or venlafaxine XR (titrated to a target dose of 150 mg/d) for 12 weeks. Those who were sexually active at baseline (n = 193) and those who, in addition, achieved remission (n = 111) were defined a priori for analyses of change in sexual function. Treatment-emergent sexual dysfunction was significantly less prevalent among patients who received agomelatine, and venlafaxine XR was associated with significantly greater deterioration on the Sex Effects Scale domains of desire and orgasm. Both treatments resulted in equivalently high rates of remission (agomelatine, 73%; venlafaxine XR, 66.9%), although fewer patients in the agomelatine group discontinued treatment because of adverse events (agomelatine, 2.2%, vs venlafaxine XR, 8.6%). Agomelatine seems to be an efficacious antidepressant with a superior sexual side effect profile compared with venlafaxine XR, although superiority to placebo was not evaluated in this trial.

Agomelatine in the treatment of major depressive disorder

To demonstrate the clinical effectiveness of an antidepressant drug requires evidence beyond short- and long-term efficacy, including a favourable adverse-effect profile and sustained treatment adherence. Under these conditions, patients should experience enhanced social and functional outcomes. The novel antidepressant agomelatine, a melatonergic MT1/MT2 receptor agonist with serotonin 5-HT2C receptor antagonist activity, displays antidepressant efficacy with a favourable adverse-effect profile that is associated with good patient adherence. Specifically, agomelatine has demonstrated significant short-term (6–8 weeks) and sustained (6 months) antidepressant efficacy relative to placebo, as well as evidence of relapse prevention (up to 10 months). In head-to-head comparative studies with venlafaxine and sertraline, there was evidence of early (at 1–2 weeks) and sustained (at 6 months) advantages for agomelatine. In addition to evidence of early efficacy, agomelatine also restored disturbed sleep-wake patterns early in treatment. There was no evidence of antidepressant-induced sexual dysfunction, weight gain or discontinuation-emergent symptoms. Agomelatine has demonstrated a range of properties that suggest it could offer advantages over current treatments for major depressive disorder, although further comparative trials are still required, as is evidence from real-world clinical practice.

How well do psychosocial interventions work in bipolar disorder

Objective: Although medication is the mainstay of treatment for bipolar disorder, several adjunctive psychosocial interventions have been manualized over the last decade. This papers objective is to empirically evaluate the different treatment approaches. Method: We conducted a systematic review of the recent literature pertaining to psychosocial interventions in bipolar, using MEDLINE and PsycINFO. Bibliographies of papers were scrutinized for further relevant references. Articles published from 1999 up to and including 2006 were reviewed. Randomized controlled trials were emphasized. Conclusions: Although psychological models of bipolar disorder fail to inform the psychotherapy treatment to the same extent as in unipolar depression, manualized adjunctive, short-term psychotherapies have been shown to offer fairly consistent benefits to bipolar disorder patients. Cognitive-behavioural therapy, family-focused therapy, and psychoeducation offer the most robust efficacy in regard to relapse prevention, while interpersonal therapy and cognitive-behavioural therapy may offer more benefit in treating residual depressive symptoms.

The Relationship between Testosterone and Sexual Function in Depressed and Healthy Men

AIM Men with Major Depressive Disorder (MDD) report high rates of sexual dysfunction, as do healthy males with low levels of testosterone. The objective of this study is to evaluate the effects of depression and low testosterone across various domains of sexual function. METHODS Untreated depressed males (N = 44) and age-matched healthy controls (N = 50) had blood samples drawn to determine morning levels of total testosterone (TT) and bioavailable testosterone (BT). In addition, questionnaires regarding depressive symptoms as well as sexual function were administered. MAIN OUTCOME MEASURES Sexual function outcomes were measured using the Sex Effects (SexFX) Scale and depression severity was assessed with the Hamilton Rating Scale for Depression-17 item (HAMD-17). RESULTS Using TT criteria, 27.9% of men were categorically defined as hypogonadal compared to 19.3% using BT criteria. Within both TT and BT hypogonadal groups, men with MDD had lower scores on all domains of sexual function compared to healthy controls with hypogonadism. Testosterone levels interacted with MDD status to affect orgasm and desire, although not arousal. Multiple linear regression analyses revealed that depression status was the main factor influencing sexual function. Hypogonadal status was not a predictor of sexual function in this sample, although age did play a minor role in the domain of arousal. CONCLUSION While testosterone levels appear to influence sexual function, specifically orgasm, the presence of MDD appears to be a stronger factor and has high predictive value for sexual outcomes.

Neurostimulation therapies for treatment resistant depression: A focus on vagus nerve stimulation and deep brain stimulation

Antidepressant treatments, including pharmacotherapy and psychotherapy, do not result in remission for the majority of patients with major depressive disorder. The high prevalence of treatment resistant depression (TRD) poses a significant issue for patients as well as both societal and economic costs. Due to the limited efficacy of existing therapies in this sub-population, alternative somatic treatments are being explored. Both vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are neurostimulation treatments for TRD. While VNS has Food Drug Administration approval as an adjunctive therapy for MDD, DBS is still in the experimental stages. This article will review the evidence supporting the clinical utility of these therapies.

Instruments to measure sexual dysfunction in community and psychiatric populations

Sexual dysfunction is a significant issue for many individuals. This can be the result of existing disorders, side effects of medications, or both. In order to effectively assess and, if appropriate, manage sexual dysfunction in various populations, it is important to consider the use of validated instruments that can provide a baseline to detect dysfunction and measure change over time. This review will assess the psychometric properties of scales (self-report and interview-based) that have been used in community, psychiatric, and gender-specific populations, with a particular emphasis on depressed patients before and during antidepressant therapy. Key considerations for scale selection and development are also discussed.

The effects of agomelatine on sexual function in depressed patients and healthy volunteers

Selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor antidepressants are associated with high rates of treatment‐emergent sexual dysfunction (TESD) due to stimulation of serotonin receptors.