European guideline for the diagnosis and treatment of insomnia

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

Lack of seasonal variation of symptoms in patients with chronic fatigue syndrome.

Several of the symptoms involved in chronic fatigue syndrome (CFS) such as fatigue, hypersomnia, hyperphagia, weight gain, and mood show seasonal variations in the general population. The aim of this study was to investigate whether patients with CFS experience seasonal fluctuations in these symptoms as well. Seasonal variation of symptoms was assessed in a group of 41 patients with CFS and 41 controls closely matched for age, gender, and city of residence. Participants were recruited across the US and were asked to complete the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Profile of Mood States (POMS). CFS patients showed significantly lower scores on multiple SPAQ-derived measures as compared with controls. These included seasonal variation in energy, mood, appetite, weight, and sleep length. Patients also reported a significantly reduced sensitivity toward sunny, dry, and long days than controls. No association was noted between intensity of seasonal changes and severity of depressive symptoms. Patients with CFS exhibit an abnormally reduced seasonal variation in mood and behavior and would not be expected to benefit from light therapy.

Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms.

BACKGROUND: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. METHODS: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. RESULTS: Meta-chlorophenylpiperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. CONCLUSIONS: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.

Hormonal responses to the administration of m-chlorophenylpiperazine in patients with seasonal affective disorder and controls.

We report on the plasma cortisol and prolactin responses to the serotonergic agonist m-CPP (0.1 mg/kg) in 10 patients with winter seasonal affective disorder (SAD) and 10 controls during the winter, in both untreated and bright light-treated conditions; and on 8 other SAD patients and 8 other controls during the summer. Following m-CPP infusion, untreated patients had exaggerated prolactin (p < .05) and cortisol (p < .05) responses compared to controls. Light treatment significantly reduced responses of both hormones to m-CPP (prolactin: p < .01; cortisol: p < .01). When untreated winter subjects and summer subjects were compared, cortisol, but not prolactin responses to m-CPP were found to be higher in patients than in controls during the winter, and lower in patients than in controls during the summer (diagnosis by season: p < .05). These results are consistent with those of our previous report on the behavioral responses to m-CPP in the same patients and suggest an abnormality in serotonergic function in untreated SAD patients in winter, which is normalized following treatment with light therapy and naturally during the summer.

Platelet [3H]paroxetine binding, 5-HT-stimulated Ca2+ response, and 5-HT content in winter seasonal affective disorder.

The present study was designed to evaluate cellular serotonergic functions in winter seasonal affective disorder (SAD) using serotonin (5-HT)-stimulated Ca2+ response as an integrated measure of 5-HT2 receptor function in platelets, [3H]paroxetine binding to characterize the platelet 5-HT transporter and 5-HT content as an index of the platelet storage capacity for this neurotransmitter amine. Purified density-dependent subpopulations of platelets in untreated and light-treated SAD patients and matched controls were investigated in order to control for possible variations in platelet turnover. We found no differences between SAD patients and controls on any of the measures, nor between light therapy conditions in SAD patients, although we found a higher Bmax of [3H]paroxetine binding and 5-HT content in heavy platelets compared to light platelets. Although the validity of platelet serotonergic measures as a model for brain serotonergic systems still remains to be elucidated, we found no evidence of platelet serotonergic abnormalities in our sample of SAD patients.