Deficits in Memory after an Episode of Depression May Improve with Modafinil

After an episode of depression, almost half of the patients have impaired cognition (executive functioning, memory, attention), which results in poorer functioning and higher risk of relapse. in a study published in Biological Psychiatry CNNI, Muzaffer Kaser and colleagues suggest that modafinil improves memory in those patients. Modafinil is a a wake-promoting agent approved by the FDA for the treatment of narcolepsy and shift work sleep disorder. In a double-blind, randomized study, they compared two groups patients in remitted depression (30 who took a single-dose of 200 mg modafinil vs. 30 who took a single dose of placebo) for cognition and fatigue .

They found that modafinil improves episodic and working memory but has no effect on attention, planning, or fatigue. They hypothesize that patients recovering from depression have a dysfunction in the hippocampal areas of the brain. Modafinil could improve memory by releasing the neurotransmitter glutamate in the hippoccampus.

Bright Light Therapy for Non-Seasonal Depression

Bright light therapy is a safe and effective treatment for seasonal affective disorder, a depression characterized by depressed mood and vegetative symptoms (increased sleep and appetite, decreased energy and motivation) during winter months. Two recent studies suggest that bright light therapy can also be used in the treatment of non-seasonal depression. In a study published in 2015 in the Journal of Clinical Psychiatry, Dr. Özdemir and collaborators conducted an 8-week study comparing 150 mg venlafaxine Extended Release (ER) with (25 patients) or without (25 patients) light therapy (60-minute light of 7000 lux the initial week of clinical management (venlafaxine + bright light therapy) daily at 7:00 AM) in non-seasonal major depressive disorder. They found that venlafaxine+light therapy is more effective and works more quickly than venlafaxine alone to improve mood. In a more recent study published in 2016 in JAMA Psychiatry, Dr. Lam and collaborators conducted a randomized, double-blind, placebo-controlled study in patients with non-seasonal depression treated with either light therapy alone (32 patients), light therapy combined with 20 mg of  fluoxetine (29 patients), fluoxetine alone (31 patients) or placebo (30 patients). The light therapy consisted of 8-week, 30-minutes (if possible bewteen 7 and 8 am), daily exposure to a 10,000-lux fluorescent white light box light box. Patients treated with light monotherapy or light combined with fluoxetine had more improvement in depressive symptoms than patients treated with fluoxetine alone or placebo. Thus, both studies suggest that light therapy is well tolerated and more effective than an antidepressant alone for the treatment of non-seasonal depression. Larger studies will be necessary to corroborate these results.

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.