Current Psychiatry Reviews - Volume 9, Issue 4, 2013

Among the numerous forms of comorbid mental health and substance use disorders, co-morbidity between alcohol use disorders (AUD) and depression has received considerable attention. AUDs and depression co-occur at levels greater than expected by chance in clinical and epidemiological samples. Studies suggest that about 80% of patients with AUD experience depressive symptoms at some stage in their lives including 30% or more who describe significant depression which lasts for weeks and which meets criteria for a major depressive episode. Several hypotheses have been proposed to explain why the two disorders co-occur in individuals at higher than expected rates. There is also emerging evidence to suggest that pharmacological treatment of depressive symptomatology as an adjunct to treatment for alcohol dependence may be effective not only in treating depression but also in reducing alcohol consumption and alcohol related harm. This review explores the literature on the epidemiology, etiology and management of depression and co-morbid AUD. It also identifies the areas for further research.

Deficits in social functioning are prevalent in individuals with schizophrenia and can often be as debilitating as the illness itself. Recent research has suggested that problems in social functioning can be seen long before the onset of schizophrenia and are generally present throughout the course of the disease. Recent literature on social functioning is critically reviewed for high-risk groups, first-episode psychosis, and later schizophrenia. Deficits in social functioning begin as early as childhood and often continue throughout the course of schizophrenia. However, social functioning can stabilize or even improve later in the course of the illness. Implications and directions for future research are discussed.

Sexual dysfunction is a common symptom in patients with depression and a frequent, poorly tolerated side effect of antidepressants used in treating their condition. The severity of this impairment can lead to non-adherence to the very medications prescribed for these patients and interfere with their recovery. Antidepressant-associated sexual dysfunction reduces patients’ quality of life and therapeutic efficacy, yet physicians may not appreciate the prevalence of this side effect and how severely it can affect treatment adherence. In untreated patients with depression, the incidence of sexual dysfunction can be very high, but estimates have varied widely depending on the assessment method used, and evaluation of global sexual dysfunction (35–45%) versus specific phases of the sexual function cycle (60–80%). This paper provides a brief overview of current sexual dysfunction assessment tools. Patient factors and antidepressant selection affecting patient adherence are reviewed and the potential for individualized antidepressant treatment is discussed. The paper also offers potential options, including genetic identification, for managing antidepressant-associated sexual dysfunction in the hopes of improving patient adherence and treatment success.

Though the basic pathophysiology of psychosis is largely unknown, there is reliable evidence that genes contribute to its aetiology. Epidemiologic studies suggested that chronic use of cannabis is a risk factor for the development of psychosis. Recent researches have focused on the identification of genetic variants that moderate the effect of cannabis on psychosis occurrence. We undertook a systematic review of primary studies that reported the direct measures of genetic risk in the association between cannabis use and psychosis considering cannabis use as an environmental factor under the gene-environment interaction model. The initial search from PubMed revealed 187 records, of which 113 were excluded on reading the abstract. Of 74 papers screened in full, 60 were reviews, 14 were included for data extraction. We report a structured summary of populations studied, study design, evaluations of cannabis use, genetic variations, outcome measures and main results. The 14 primary studies included in the survey applied the candidate gene approach, COMT being the most investigated; also CNR1, BDNF and SLC6A4 were examined; a novel candidate gene, AKT1, was identified through a multistage approach. Few candidate genes were investigated, and reliable replications were provided only for AKT1. Studies were heterogeneous in terms of experimental design and outcome measures, thus hampering an effective synthesis. We conclude that additional primary studies are warranted. An effort in harmonisation of data, coupled with the recent advances in genetic technologies, should be encouraged.

Background: All antipsychotic agents marketed since clozapine have been categorized as “atypical”, without regard for the true definition of “atypicality”. The standard practice of designating every new agent as “atypical” not only ignores the definition, but conveys a false sense of safety for the majority of these medications when considering the risks of movement disorders, both acute and latent. Though receptor profiles are unique to each medication, the antipsychotic effect of all agents is attributed to reducing dopamine activity in the mesolimbic area, usually through the blockade of dopamine type 2 (D2) receptors, whether the agent is “tightly” or “transiently bound”. Yet, antagonism of D2 receptors in the striatum is associated with the potential for extrapyramidal symptoms (EPS), as well as the development of tardive dyskinesia (TD). Clozapine is categorized as “atypical” because its use is not associated with EPS or TD at a rate greater than placebo, as it provides antipsychotic efficacy at a lower saturation of D2 receptors than traditional antipsychotics. As newer second-generation agents came to market, the definition of “atypical” has been modified to include a variety of characteristics unrelated to movement side effects. Nevertheless, many clinicians still assume that “atypicality” indicates a risk of EPS and TD at no-greater-than-placebo rates. Objective: This paper examines each of the 10 second-generation agents approved in the United States for treatment of schizophrenia (and cariprazine, for which approval is pending), and examines which ones meet the strict definition of “atypical” (ie, risk of EPS and TD no greater than placebo). Data source: A literature search using PubMed and Google Scholar, involving various combinations of the keywords “antipsychotic,” “atypical,” “typical,” “first generation,” “second generation,” “schizophrenia,” “tardive dyskinesia,” “movement disorders,” and “extrapyramidal symptoms,” in addition to the 11 agents by chemical name, yielded a vast set of clinical trials, systematic reviews, case reports, and receptor-profile studies. These articles and reports were narrowed to the appended reference list, based on the report’s/trial’s contribution to the discussion of “atypicality.” Results/Conclusions: Of the 10 second-generation agents currently in use, and the one awaiting approval, only clozapine, quetiapine, and iloperidone meet the criteria necessary for the designation of “atypical” (ie, rates of EPS and TD no greater than placebo).

Depression and anxiety are common during pregnancy. Depression is associated with preterm birth, low birth weight, and intrauterine growth restriction. Risk factors related to depression and anxiety during pregnancy are poor social support, poor quality of intimate relationship, poverty and previous episodes to depression and anxiety. When these mental disorders are untreated, poor health behaviors are observed in pregnant patients including inadequate nutrition, smoking, drug use and failure to attend medical appointments. Inadequate maternal-fetal attachment is developed when mother is depressed. Self-harm is another situation of concern in depressed pregnant women. On the other side associated risks to antidepressant and anxiolytic treatment during pregnancy have to be considered, it has been reported miscarriage, perinatal death, lower birth weight, preterm birth and lower Apgar scores related to psychotropic drug use during pregnancy. Increased risk of malformation is still controversial, as well as developmental effects in children of mothers exposed to of psychotropic drugs. In this review we explore literature related to depression and anxiety during pregnancy to weigh risk and benefits of their treatment in the mother and the baby.

Objective: To review current literature on the effectiveness of preventive antidepressant treatment in patients with Chronic Hepatitis C (CHC) treated with pegylated interferon (IFN)-alpha and ribavirin. Methods: We identified studies published from 2001 to May 2013 that evaluated the effectiveness of preventive antidepressant use in patients with CHC treated with IFN. We excluded studies that focused on symptomatic treatment. Results: Nine studies were found. Five of the nine clinical trials reported positive effects of an antidepressant agent in the prevention of IFN induced depression. Two yielded negative results, and one had inconclusive findings. Three studies had either no control arms, or did not include any information about randomization or blinding. Nearly all of the studies excluded patients with previous psychiatric history. Most of the early studies had limited sample sizes. Only two studies reviewed had a sample size larger than 100 patients. Follow-up period varied broadly in the different studies, ranging from 12 to 72 weeks. The two studies with the largest samples yielded contradictory results. The effect sizes ranged widely, some studies showed marginal improvement, and others found a highly significant improvement in the prevention of interferon induced depression. Patient attrition was high in most of the studies, and was similar in treatment and control arms. Conclusions: Data on the effectiveness of preventive antidepressant use for IFN induced depression in CHC patients is limited and inconclusive. There is still a clear need for further studies with larger sample sizes and rigorous methodology to draw conclusions and make a clear recommendation for preventive antidepressant treatment in all CHC patients receiving IFN.

Background: A reciprocal association exists between Major Depressive Disorder (MDD) and Coronary Heart Disease (CHD). A quantitative evaluation of this association is necessary to identify potential areas of clinical intervention. However, the association is unclear because of methodological differences and confounders across studies. This review examines the impact of methodology and confounding variables on the magnitude of the relationship between MDD and CHD. Methods: The search terms “major depression AND coronary heart disease” were entered into an electronic multiple database search engine. Abstracts were screened for relevance and individually selected articles were collated. Results: Nine methodological issues and three confounders are identified, which have contributed to uncertainty in the quantitative relationship between MDD and CHD. More quantitative, prospective longitudinal studies are needed, which use standard definitions for MDD and CHD and define clear outcomes. Studies should clearly establish the temporal relationship between the onset of depressed mood and one or more adverse cardiac events, should use quantitative measures of depression which are treated as continuous data, and have frequent measures of mental state over time, correlated with measures of cardiac health. Study design should avoid confounding by considering demographic factors, cardiac risk factors and management of MDD in CHD patients. Conclusions: This review raises the need for a standardised methodology in future research, taking into account the biases and confounders listed. Adopting a consensus approach to methodology will facilitate the quantitative exploration of the causal network linking MDD and CHD.

Objective: This article provides an up-to-date review of major drug interactions and an overview of food interactions with monoamine oxidase inhibitors (MAOI) including both antidepressants and other drugs used in general medicine. Data Sources: English language literature identified by PubMed search of terms including monoamine oxidase, phenelzine, tranylcypromine, isocarboxazide, selegiline, rasagiline, linezolid, methylene blue, serotonin syndrome, hypertensive crisis. Articles were selected primarily from the last 10 years of published journals with a selection of classical older articles. Exclusion criteria were not applied because of the interest in including case reports of drug interactions. Data Extraction: type, frequency, and severity of drug interactions. Results: Classical irreversible non-selective monoamine oxidase inhibitors (MAOI) (phenelzine, tranylcypromine, and isocarboxazid) have been minimally utilized due to fear of dietary and drug interactions. Moclobemide and transdermal selegiline offer greatly improved safety and comparable psychiatric efficacy, while non-psychiatric MAOIs such as linezolid, methylene blue, oral selegiline and rasagiline have similar potential drug interactions. The most hazardous MAOI drug interactions involve SSRI and SNRI antidepressants, meperidine, tramadol, dextromethorphan and sympathomimetics while the food interactions involve high tyramine aged fermented foods. Conclusions: Awareness of hazardous MAOI drug interactions is essential both in using these drugs for treatment of depression and in general medical consultation.