Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants do not Increase the Risk of Cardiovascular Problems

There is some controversy on whether antidepressants increase or reduce the risk of cardiovascular problems (myocardial infarction, stroke or transient ischemic attack, arrhythmia). To address this issue, Coupland and colleagues report the results of an observational study on 238 963 patients aged 20 to 64 years with a first diagnosis of depression. In a five-year follow-up, there was no evidence of an association between SSRI’s and an increased risk of arrhythmia or stroke/transient ischemic attack. The risk of arrhythmia and myocardial infarction seems to be reduced with some selective SSRI’s, particularly fluoxetine. In contrast, an older class of antidepressants, the tricyclics, increase the risk of arrhythmia in the first 28 days of treatment, with the tricyclic lofepramine having the highest risk of cardiovascular problems in the first year of follow-up. The authors conclude that the results are reassuring in light of recent concerns regarding the cardiovascular effects of antidepressants.

N-Acetylcysteine for Excoriation (Skin Picking) Disorder, Trichotillomania (Hair Pulling), and Obsessive Compulsive Disorder

Skin picking disorder is a disabling condition which consists of repeated picking of the skin leading to noticeable skin damage. It affects up to 5% of the population and no medication seems to be effective for the treatment of this disorder.

In a study published in the 3/23/2016 online issue of JAMA Psychiatry, Grant and colleagues report a decrease in skin-picking symptoms in a randomized double-blind 12-week study comparing 31 patients on placebo with 35 patients on N-acetylcysteine in a dosing range of 1200-3000 mg daily. N-acetylcysteine was well tolerated. Side effects were mild and included nausea (14% of participants]), dry mouth (3%), constipation (6%), and dizziness (3%). In a previous study, the same group found that N-acetylcysteine is also effective for the treatment of tricholamania, a condition characterized by a compulsive urge to pull out one’s hair resulting in hair loss, balding, and distress. Afshar and colleagues reported the effectiveness of N-acetylcysteine as an add-on treatment for refractory obsessive-compulsive disorder (OCD) treated with selective-serotonin-reuptake-inhibitor antidepressants.

N-acetylcysteine is an amino acid available without prescription. The authors hypothesize that N-acetylcysteine decreases compulsive behaviors by increasing extracellular levels of glutamate in the nucleus accumbens. Because skin-picking, trichotillomania, and OCD are chronic conditions, a treatment longer than 12 weeks may be necessary. Cognitive Behavioral Therapy (CBT) is also beneficial and should be combined with N-acetylcysteine.

Genetic Testing to Determine Responses and Side Effects to Psychotropic Medications

Genetic testing as an additional measure to determine responses and side effects to psychotropic medications is now available in my private practice. The Genecept Assay is a simple, non-invasive, buccal test developped by Genomind. It analyzes ten genes shown to have implications for response to treatments used in depression, bipolar disorder, schizophrenia, anxiety disorders, OCD and ADHD. The analyzed genes target major hepatic enzymes and key neurotransmitter pathways including serotonin, dopamine and glutamate.


For more information or to schedule an appointment, call (917) 251-6498. 

Naltrexone as a Possible Treatment for Decreasing Cannabis Use

According to a SAMHSA survey, 19.8 million individuals or 7.5% of the US population were current (past month) users of marijuana in 2013. Among people age 18 to 25, current use reached 19.1%. Given the widespread consumption of marijuana, it becomes imperative to develop new therapeutic approaches to decrease its use. In a double-blind, placebo-controlled laboratory study, Dr. Haney and colleagues assessed the effects of 50 mg of naltrexone on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Daily cannabis users were treated with either naltrexone 50 mg daily (n=23) or placebo (n=28) for 16 days and were assessed for 4 to 6 weeks. Compared to the placebo group, the naltrexone group significantly used less cannabis and had less positive subjective effects from cannabis. Although naltrexone was associated with decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, dropout rates were similar between groups. Based on their findings, the authors conclude that “naltrexone may reduce ongoing heavy cannabis use, relapse severity, or the likelihood that patients would return to pretreatment levels of heavy cannabis use in the event of a lapse.”

Is Mirtazapine Superior to Other Antidepressants?

Previous studies suggest that mirtazapine has a better efficacy and faster onset of action than other antidepressants (for a review, see Watanabe et al, 2011). Mirtazapine also differs from SSRIs (e.g., fluoxetine, paroxetine, sertraline, citalopram, fluvoxamine) by its side effect profile. It has a higher risk of dry mouth, weight gain or increased appetite, fatigue and somnolence but less risk of sweating, diarrhea, nausea or vomiting, sexual dysfunction, headache, tremor and sleep disturbance. Ueno and colleagues also report that a dose increase of mirtazapine after one week of treatment is an effective strategy in early non-improvers with depression. Thus, these studies suggest that mirtazapine should be considered as a first-line treatment for depressive disorders. However, patients may be concerned by the risk of weight gain and somnolence, and therefore may prefer to be treated with another antidepressant.

Augmentation Therapy for Treatment-Resistant Depression

Dr. Zhou and colleagues conducted a meta-analyses on 48 randomized controlled trials (total of 6654 participants) of augmentation agents in adults with treatment-resistant depression. According to the network meta-analysis, the best agents for augmentation therapy were quetiapine, aripiprazole, thyroid hormone, and lithium. Although thyroid hormone and lithium are better tolerated, they seem to be less efficacious than quetiapine and aripiprazole. The authors acknowledge that further studies comparing these augmentation agents head-to-head and addressing the limitations of previous studies (e.g., longer duration, dosing, sample size, study design, financial bias) will be required to confirm these results. In a commentary, Dr. Richard Shelton discusses about the limitations of meta-analyses and suggests interpreting these results with caution.

Antidepressant Treatment in Individuals with Burnout

Burnout is a state of emotional exhaustion related to chronic stress from work or personal issues. Madsen and colleagues found that burnout is associated with an increased risk of antidepressant treatment in 2936 Danish human service workers. As noted by the authors, these results suggest that individuals with high levels of burnout are at substantial risk of developing a clinically significant mental health condition that may require antidepressant treatment.