SOURCE: MPR
September 29, 2014

The world’s most expensive spice may also be an alternative treatment for mild-to-moderate depression, according to a new study published in the journal Human Psychopharmacology. Saffron, the spice derived from the flower of Crocus sativus, has been found to have had anticancer, anti-inflammatory, antioxidant, and antiplatelet effects in previous research and recent clinical trials have suggested that it could also be used for the prevention and treatment of Alzheimer’s disease. This review analyzed six clinical trials on the efficacy and safety of saffron in the treatment of major depressive disorder in 230 adult outpatients 18–55 years of age. In two randomized, double-blind, placebo-controlled studies, 30mg/day of C. sativuswas found to be effective for the treatment of mild-to-moderate depression; 30mg/day of extract of saffron stigma was also found to be as effective as fluoxetine 20mg/day and imipramine 100mg/day for the treatment of mild-to-moderate depression in other studies. Additional research is needed to better understand the mechanisms associated with saffron as a therapy for major depressive disorder as well as developing an optimal treatment schedule, including dose and length of therapy.

SOURCE: HealthDay News
September 2014 | Mary Elizabeth Dallas

Significantly lower levels of a key estrogen receptor may play a role in autism spectrum disorders, according to a new study.

This link between autism and sex hormones could help explain why the condition is about four times more common among men than women, the researchers noted.

"Our study is the first indicator that estrogen receptors in the brain of autism spectrum disorder patients may be different to controls," study author Anilkumar Pillai, from Georgia Regents University, said in a news release. "Though this suggests a possible reason for the gender bias, we still need to determine what causes the reduced production of estrogen-related proteins."

Autism spectrum disorders refer to a group of disorders that affect brain development. Signs and symptoms of autism include impaired social interaction and communication skills as well as restricted and repetitive behavior.

For the study, published Sept. 9 in the journal Molecular Autism, the researchers compared the brains of 13 people with autism to 13 people who didn't have the condition. The difference they found was in the brain's estrogen signaling.

Specifically, the researchers measured levels of an estrogen receptor molecule known as ERβ in the participants' brains. They also measured levels of aromatase, an enzyme that converts testosterone to estradiol, the most potent estrogen.

The study revealed the brain tissue of those who had autism had 35 percent less ERβ mRNA and 38 percent less aromatase mRNA. This could affect the conversion of testosterone to estradiol, increasing testosterone levels.

The researchers noted their study was small, and said more research is needed to explore how changes in estrogen signaling are related to autism.

"It is worth looking at whether drugs which modulate estrogen reception, but do not cause feminization, could allow for the long-term treatment of male patients with autism spectrum disorders," said Pillai. "Current treatment involves the use of antipsychotics, which has long been a major concern as these patients are typically still in a stage of life where brain development is very rapid. However, additional studies are needed to test the estrogen mechanism."

SOURCE: DocGuide
March 2015

BACKGROUND 
Sleep disorders are frequently associated with childhood behavioral problems and mental illnesses such as anxiety disorders. To identify promising behavioral targets for therapy of pediatric anxiety disorders, we investigated the associations between specific sleep and behavioral problems.

METHODS 
We conducted retrospective reviews of 105 patients aged 4-12 years who met the DSM-IV criteria for primary diagnosis of generalized anxiety disorder (GAD; n = 33), separation anxiety disorder (SAD;n = 23), social phobia (SP; n = 21), or obsessive-compulsive disorder (OCD;n = 28). Sleep problems were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) and behavioral problems by the Spence Children's Anxiety Scale (SCAS), Oppositional Defiant Behavior Inventory (ODBI), and Depression Self-Rating Scale for Children (DSRS-C).

RESULTS 
Depressive behavior was weakly correlated with CSHQ subscores for sleep onset delay and night waking but not with total sleep disturbance. Anxiety was correlated with bedtime resistance, night waking, and total sleep disturbance score. Oppositional defiance was correlated with bedtime resistance, day time sleepiness, sleep onset delay,and most strongly with total sleep disturbance.Multiple regression analyses revealed that OBDI score had the strongest positive association with total sleep disturbance and the strongest negative association with total sleep duration.

CONCLUSIONS 
Sleep problems in children with anxiety disorders are closely related to anxiety and oppositional defiant symptoms.

SOURCE: MPR
February 2015

Merck announced that Belsomra (suvorexant) tablets are now available for the treatment of insomnia in adults who have difficulty falling asleep and/or staying asleep. Belsomra has been scheduled as a CIV controlled substance due to its abuse and dependence potential.

Belsomra is the first orexin receptor antagonist approved for the treatment of insomnia. The mechanism by which it exerts its therapeutic effect in insomnia is presumed to be through antagonism of orexin receptors. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.

Drug name: Belsomra
Generic Name and Formulations: Suvorexant 5mg, 10mg, 15mg, 20mg; tabs.
Company: Merck & Co., Inc.

Therapeutic Use: Sleep-wake disorders

Indications for BELSOMRA: Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Adult: Use lowest effective dose. Take within 30 mins of bedtime if able to get full night’s sleep (≥7hrs) before awakening. 10mg once per night; may increase if ineffective; max 20mg once daily. Concomitant moderate CYP3A inhibitors: 5mg once daily; max 10mg once daily. Effect may be delayed if taken with or soon after a meal.

Children: Not established.

Pharmacological Class: Orexin receptor antagonist.

Contraindications: Narcolepsy.

Warnings/Precautions: Monitor for somnolence and CNS depression; discontinue or reduce dose if daytime somnolence develops. Risk of next-day impairment (including impaired driving). Monitor for worsening insomnia or abnormal thinking and behavioral changes. Consider discontinuing if any complex sleep behaviors develop. Depression. Monitor for suicidal ideation. Compromised respiratory function (eg, COPD, obstructive sleep apnea). Increased risk of exposure-related effects in obese women. Reevaluate if unresponsive after 7–10 days of treatment. Severe hepatic impairment: not recommended. Drug or alcohol abusers. Pregnancy (Cat.C). Nursing mothers.

Interactions: Avoid alcohol. Potentiates CNS depression with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol); may need to adjust doses. Concomitant strong CYP3A inhibitors (eg, ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, conivaptan): not recommended. Concomitant moderate CYP3A inhibitors (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil); use reduced dose (see Adults). May be antagonized by strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin). Monitor digoxin.

Adverse Reactions: Somnolence, headache, dizziness; CNS depression, daytime impairment, complex sleep-related behaviors (eg, sleep-driving), sleep paralysis, hallucinations, cataplexy-like symptoms.

Generic Availability: NO

How Supplied: Blisters—30

SOURCE: DocGuide
January 2015 | European Archives of Psychiatry and Clinical Neuroscience

SOURCE: MPR

SOURCE: MGH Center For Women's Mental Health 
August, 2014 | Ruta Nonacs, MD PhD

While many midlife women are interested in pursuing non-hormonal options for the treatment of menopausal symptoms, they are understandably concerned about taking antidepressant medications, such as SSRIs and SNRIs, that, while effective for treating hot flashes and night sweats, are commonly associated with sexual side effects. A recent study indicates that venlafaxine (Effexor, an SNRI antidepressant) does not differ significantly from estradiol in terms of its effects on sexual functioning.

In an 8-week randomized controlled trial among women aged 40–62 years, sexual function was compared in women receiving 0.5 mg oral estradiol per day, 75 mg venlafaxine per day, or placebo. Overall sexual functioning among non-depressed midlife women with hot flushes did not change over the 8 weeks of treatment with either low-dose oral estradiol or venlafaxine (compared with placebo). However, there may be a subtle increase in desire among women taking estradiol and a decreases in orgasm and pain among women taking venlafaxine.


Reference

Reed SD, Mitchell CM, Joffe H, Cohen L, et al. Sexual function in women on estradiol or venlafaxine for hot flushes: a randomized controlled trial. Obstet Gynecol. 2014 Aug; 124:233-41.

SOURCE: DocGuide
May 21, 2015 | Louise Gagnon

Patients with depression and have increased salivary cortisol levels fail to respond to treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine, according to a study presented here at the 168th Annual Meeting of the American Psychiatric Association (APA).

Previous research linked elevated levels of cortisol, also referred to as the stress hormone, to resistance to antidepressant treatment, explained Raul Ventura-Junca, MD, PhD, Universidad de Chile, Santiago, Chile, on May 17.

Researchers enrolled 208 patients, 187 with normal thyroid function and 21 noneuthyroid. The diagnosis of depression and the severity of illness were determined by the Mini-International Neuropsychiatric Interview and the Hamilton depression scale (HAM-D17).

The patients with normal thyroid function were treated with fluoxetine (20 mg). Of the 166 patients who started treatment with fluoxetine, 145 continued to 3 weeks of treatment, and 122 continued to the end of 8 weeks of drug therapy.

Of the 122 patients, the 67 who responded to treatment and 48 who remitted all had significantly lower circadian basal salivary cortisol levels than nonresponders (P = .008 and .021, respectively).

“We can conclude that higher cortisol levels are a predictor of resistance to fluoxetine treatment,” said Dr. Ventura-Junca. “If you measure circadian cortisol levels, and patients have elevated cortisol, you should not begin to treat them with either 20 or 40 mg of fluoxetine treatment. You should consider an alternative.”

Salivary cortisol levels remained stable with fluoxetine treatment.

Patients who chose to discontinue treatment before the third week of the study showed reduced levels of salivary cortisol (P = .057), said Dr. Ventura-Junca, speculating that the patients were very good responders to the SSRI.

“We think that these people did not abandon treatment early because of side effects of treatment but because they were already feeling better,” concluded Dr. Ventura-Junca, adding that other factors are likely involved in response to fluoxetine.

[Presentation Title: Cortisol Levels Before and After Antidepressant Fluoxetine Treatment in Chilean Patients With Major Depressive Disorder. Abstract P3-052]

SOURCE: DocGuide
May 21, 2015 | Louise Gagnon

Prazosin is effective in managing sleep disturbance and improving sleep quality, symptoms that are associated with posttraumatic stress disorder (PTSD), according to a study presented here at the 168th Annual Meeting of the American Psychiatric Association (APA).

"It is a medication that is used to treat conditions like high blood pressure and benign prostatic hypertrophy," explained Davit Khachatryan, MD, MHSC, Queen's University, Kingston, Ontario, Canada, on May 16. "There has been a reaction in terms of decreasing startle response, which is a key feature of PTSD. It is a medication that suppresses the noradrenergic stimulation, and in doing that, it suppresses the startle response."

The medication is prescribed off-label to reduce sleep disturbance, nightmares, and flashbacks, which are core symptoms of PTSD.

"There is a lack of formal evidence [with respect to prazosin use], which is why it is not considered a first-line therapy in treatment guidelines," said Dr. Khachatryan.

Dr. Khachatryan and colleagues conducted a comprehensive search using various databases. They identified 246 articles and included 6 randomised, double-blind, placebo-controlled trials that had durations of between 7 and 20 weeks. Patients included veterans, civilians, military on active duty, and a mix of populations, aged 30 to 56 years. The mean dose range of prazosin in the studies was 3.1 to 15.6 mg/day.

The researchers used a random-effect model to calculate effect sizes, which were computed as Hedges' g. They found that prazosin was superior to placebo in improving sleep quality (g = 0.987), reducing overall PTSD symptoms (g = 0.699), and decreasing sleep disturbances in particular (g = 0.799).

"These findings support the use of prazosin to treat sleep disturbances in PTSD," concluded Dr. Khachatryan, noting that his team will continue to pool data from accumulating experience of prazosin use to treat sleep disturbance linked to PTSD.

[Presentation Title: Prazosin in the Treatment of Nightmares in PTSD: Systematic Review and Meta-Analysis. Abstract P2-117]