Midday Bright Light Therapy Improves Mood in Bipolar Depressed Patients

In a six-week, double-blind study, Dr. Sit and collaborators randomly assigned adults with bipolar depression to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (23 patients in each group). The treatment was administered midday because bright light exposure at that time “can phase-advance and increase the amplitude of nocturnal melatonin production in healthy subjects and in elderly patients with insomnia.” It can also improve “decreased awake time at night, increased sleep efficiency, and reduced wake time after sleep onset.” The duration of light therapy started at 15 minutes per session between 12:00 p.m. and 2:30 p.m, increased by 15 minutes weekly up to 60 minutes by week 4. The authors found higher remission rates (68.2% vs. 22.2%) and lower depression scores with bright light therapy compared to placebo light. There were not mood polarity switches. Bright light therapy had a large effect between week 4 and week 6 of treatment. The results of this study are important given the limited treatment options for depression in bipolar disorder. In their conclusion, the authors stated “given its efficacy, ease of use, and tolerability, midday light therapy is ideally suited for depressed patients with bipolar disorder, and it may eventually gain widened acceptance with improved practitioner awareness.”

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.

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. 

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.