Melatonin May Improve Headaches

April 27, 2017 · Posted in Potential Treatments · Comment 

young woman suffering from headache

A 2016 article in the Journal of Head and Face Pain reviewed randomized placebo-controlled trials of melatonin for the treatment of headaches. Author Amy A. Gelfand and colleagues reported that 10 mg of melatonin was superior to placebo in the treatment of cluster headaches. For treatment of migraines, 3 mg of immediate-release melatonin improved headaches compared to placebo, while 2 mg of sustained-release melatonin was insufficient.

The authors also found non–placebo controlled data suggesting that melatonin may be helpful for other types of headaches. More research is needed to clarify melatonin’s effects in different headache disorders.

Clarifying the role of melatonin receptors in sleep

September 24, 2014 · Posted in Neurobiology · Comment 

sleeping mouse

The antidepressant agomelatine (which is available in many countries, but not the US) and the anti-insomnia drug ramelteon (Rozerem) both act as agonists at melatonin M1 and M2 receptors. New research is clarifying the role of these receptors in sleep.

In new research from Stefano Comai et al., mice who were genetically altered to have no M1 receptor (MT1KO knockout mice) showed a decrease in rapid eye movement (REM) sleep, which is linked to dreaming, and an increase in slow wave sleep. Mice who were missing the M2 receptor (MT2KO knockout mice) showed a decrease in slow wave sleep. The effects of knocking out a particular gene like M1 or M2 end up being opposite to the effect of stimulating the corresponding receptor.

The researchers concluded that MT1 receptors are responsible for REM sleep (increasing it while decreasing slow wave sleep), and MT2 receptors are responsible for slow wave non-REM sleep.

The new information about these melatonin receptors may explain why oral melatonin supplements can make a patient fall asleep faster, but do not affect the duration of non-REM sleep. The authors suggest that targeting MT2 receptors could lead to longer sleep by increasing slow wave sleep, potentially helping patients with insomnia.

Buspirone and Melatonin Together May Treat Unipolar Depression

January 16, 2014 · Posted in Potential Treatments · Comment 

smiling woman

The combination of the anti-anxiety drug buspirone (trade name Buspar) and melatonin, a hormone that regulates cycles of sleep and waking, may be effective for depression. Researcher Maurizio Fava and other researchers at Massachusetts General Hospital report that low-dose buspirone (e.g. 15 mg/day) combined with a 3 mg dose of melatonin produced significant antidepressant effects in a six-week study of patients with unipolar depression.

While buspirone is not a potent antidepressant at low doses, the combination of buspirone and melatonin exerted significant effects, leading to better antidepressant response than did either placebo or 15 mg of buspirone alone. Another benefit of the combination is that the low dose of buspirone minimizes side effects.

Buspirone is a serotonin 5HT1A receptor partial agonist, meaning that it produces weak activity at this serotonin receptor, but does not allow it to get overstimulated.

Depression in Youth Is Tough to Treat and Requires Persistence and Creativity

November 27, 2013 · Posted in Course of Illness, Current Treatments, Risk Factors · Comment 

teen boyAt a symposium on ketamine for the treatment of depression in children at the 2013 meeting of the American Academy of Child and Adolescent Psychiatry, David Brent, a professor at the University of Pittsburg, gave the opening talk on the fact that as many as 20% of adolescents who are depressed fail to improve, develop chronic illness, and are thus in need of alternatives to traditional treatment. Predictors of non-improvement include substance use, low-level manic symptoms, poor adherence to a medication regimen, low blood levels of antidepressants, family conflict, high levels of inflammation in the body, and importantly, maternal depression. In adolescents insomnia was associated with poor response, but in younger children insomnia was associated with a better response.

Brent suggested using melatonin and sleep-focused cognitive behavioral therapy for insomnia in youth, but not using trazodone (which is commonly prescribed). Trazodone is converted to a compound called Meta-chlorophenylpiperazine or MCPP, which induces anxiety and dysphoria. MCPP is metabolized by hepatic enzymes 2D6, and fluoxetine and paroxetine inhibit 2D6, so if trazodone is combined with these antidepressants, the patient may get too much MCPP.

Surprisingly and contrary to some data in adults about the positive effects of therapy in those with abuse histories, in the study TORDIA (Treatment of SSRI-Resistant Depression in Adolescents), if youth with depression had experienced abuse in childhood, they did less well on the combination of cognitive behavioral therapy and selective serotonin reuptake inhibitors (SSRIs) compared to SSRIs alone.