Assessing physical activity in people with mental illness: 23-country reliability and validity of the simple physical activity questionnaire (SIMPAQ).

BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.

Adjuvant Rosa Damascena has a Small Effect on SSRI-induced Sexual Dysfunction in Female Patients Suffering from MDD.

BACKGROUND: Treating major depressive disorders (MDD) with selective serotonin-reuptake inhibitors (SSRIs) may impact negatively on sexual function. On the other hand, a satisfying sexual life is associated with overall life satisfaction. Therefore, managing this negative side effect of SSRIs may have an important role in the treatment of MDD. In a former study, adjuvant Rosa damascena oil improved sexual dysfunction in male patients suffering from both MDD and SSRI-induced sexual dysfunction (SSRI-I SD). The aim of the present study was to test whether the same pattern of results would be observed among female patients suffering from both SSRI-I SD and MDD. METHOD: In a double-blind, randomized and placebo-controlled clinical trial, a total of 50 female patients (mean age: 34 years) treated with an SSRI and suffering from MDD and SSRI-I SD were randomly assigned either to the verum (Rosa damascena oil) or to the placebo condition. Patients completed self-ratings of depression and sexual function at baseline, 4 weeks later, and at the end of the study 8 weeks after its start. RESULTS: Sexual desire, sexual orgasms, and sexual satisfaction increased over time. Patients in the verum group reported decreased pain. Overall sexual score increased in the verum as compared to the placebo condition. CONCLUSIONS: Whereas in male patients suffering from both MDD and SSRI-I SD adjuvant Rosa damascena oil improved sexual function, data on female patients are less robust and suggest only modest effects on female sexual function.

Serum levels of sodium valproate in patients suffering from bipolar disorders: comparing acute and maintenance phases of mania.

OBJECTIVES: Bipolar disorders (BD) are characterized by episodes of mania and depression. There is evidence that states of psychiatric disorders impact on neurotransmitters, endocrine system and membrane transport and, therefore, it is possible that specific phases of BD differentially influence the pharmacokinetics of some drugs. The aim of the present study was to investigate the drug-disease interaction between sodium valproate, one of the major drugs used in the treatment of bipolar disorder, and acute versus maintenance states of manic episodes. METHOD: 37 patients (mean age ± SD = 37.54 ± 11.27 years; 23 males, 14 females) suffering from bipolar disorder completed the study. Blood samples were taken during both acute and maintenance states. RESULTS: Neither the trough concentration (p = 0.567) nor the internal clearances (p = 0.729) of sodium valproate in the acute phase of mania differed statistically or descriptively from those in the maintenance phase. Marginally significant phase by gender interactions were observed. CONCLUSION: No significant effect of the acute phase of mania was observed in bipolar patients and no relationship could be found between drug pharmacokinetics and disease phase. This may be explained by specific pharmacokinetic features of the drug such as low extraction ratio values. However, phase by gender interactions indicate possible gender-related issues.

Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial.

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (­18 min (P = 0.02)) and WASO (­54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.

Modafinil reduces microsleep during partial sleep deprivation in depressed patients.

OBJECTIVE: Sleep deprivation (SD) can induce a prompt decrease in depressive symptoms within 24h. Following the recovery night, however, a relapse into depression occurs in most patients. Recovery sleep, naps and even very short episodes of sleep (microsleep; MS) during SD have been shown to provoke a rapid relapse into depression. This study tested the hypothesis that modafinil reduces MS during SD and stabilizes the treatment response to PSD compared to placebo. METHODS: A total of 28 patients (13 men, 15 women; age 45.1+/-12.1 years) with a major depressive episode and a cumulative daytime microsleep of five or more minutes were investigated using a double-blind placebo-controlled study design. All patients were treated with a stable mirtazapine monotherapy. A partial SD (PSD) was performed after one week. Additional morning treatment with modafinil vs. placebo started during PSD and was maintained over two weeks. Sleep-EEG and MS episodes were recorded with a portable EEG. Depression severity was assessed using the Hamilton Depression Rating Scale before, during and after PSD and at follow-ups after one and two weeks. RESULTS: Patients treated with modafinil showed significantly reduced microsleep during PSD (11.63+/-15.99 min) compared to the placebo group (47.77+/-65.31 min). This suppression of MS was not associated with the antidepressive effect of PSD. CONCLUSIONS: Compared to placebo, modafinil was efficient in reducing daytime microsleep following partial sleep deprivation but did not enhance the antidepressive effects of PSD and did not stabilize antidepressive effects over two weeks.

Antidepressive response to sleep deprivation in unipolar depression is not associated with dopamine D3 receptor genotype.

The psychostimulant theory of antidepressive sleep deprivation (SD) proposes a contribution of dopamine D3 receptors (DRD3) in the limbic system to the antidepressant effects of SD. Neuroendocrinological studies suggest a positive correlation of clinical response to SD and cortisol secretion. We hypothesized that the clinical response to SD and amount of cortisol secretion upon SD is associated with the 1-1 genotype of the Bal1 polymorphism of DRD3 on exon 1. In this study, aiming at evaluating the feasibility of screening large patient samples, 52 inpatients (19 males/33 females) with unipolar depression and a score of 18 or more on the 21-item Hamilton Depression Rating Scale were treated with 1 night of total SD. We found that 31% of our patients responded to SD. There was no association between response to SD and the genotype of the DRD3 Bal1 polymorphism (p < 0.879). There was also no association between increase in cortisol secretion after SD and DRD3 genotypes (p < 1.000) in a subgroup of patients. Statistical power analysis ruled out a major effect of the DRD3 Bal1 polymorphism on clinical response to SD. These results suggest that the DRD3 Bal1 polymorphism is not a promising lead to be followed up in larger patient samples.

Polysomnographic effects of adjuvant ginkgo biloba therapy in patients with major depression medicated with trimipramine.

Sleep disturbance and cognitive impairment are frequent complaints of depressed patients under standard antidepressant medication. Therefore, additional therapies are required which specifically focus on the improvement of these deficits without exerting major side effects. Ginkgo biloba extract (EGb) has been shown to improve cognitive abilities in elderly subjects and in patients with disorders of the dementia spectrum. Animal studies surmise that EGb may reduce CRH activity, which is substantially related to depressive mood and behavior, predominantly cognition and sleep. An open non-randomized pilot study has been conducted to investigate the effects of ginkgo biloba extract (EGb Li 1370) on cognitive performance and sleep regulation in depressed inpatients. 16 patients were treated with a trimipramine (T)-monotherapy (200 mg) for six weeks. In eight of the 16 patients, an adjunct EGb therapy (240 mg/d) was applied for four weeks after a baseline week, the other eight patients remained on trimipramine monotherapy (200 mg) during the entire study. Polysomnography, cognitive psychomotor performance and psychopathology were assessed at baseline, after short-term and long-term adjunct EGb treatment, and after one week of ginkgo discontinuation (at the respective evaluation times in the eight patients on T-monotherapy). This report focuses on the results of EGb on sleep EEG pattern. EGb significantly improved sleep pattern by an increase of sleep efficiency and a reduction of awakenings. In addition, sleep stage 1 and REM-density were reduced, while stage 2 was increased. Non-REM sleep, predominantly slow wave sleep in the first sleep cycle, was significantly enhanced compared to trimipramine monotherapy. Discontinuation of EGb reversed most of these effects. Based on the animal data, these results suggest that EGb may improve sleep continuity and enhance Non-REM sleep due to a weakening of tonic CRH-activity. The compensation of the deficient Non-REM component in depression by the EGb application may provide a new additional treatment strategy, especially in the treatment of the depressive syndrome with sleep disturbance.

Depression and sleep disorders: clinical relevance, economic burden and pharmacological treatment.

A wide range of studies have been published over the past two decades that involve the intersection of sleep EEG, insomnia, psychiatric illness (especially depressive disorders) and psychopharmacology. Much of value has been discovered, but there have also been false starts and contradictory results. There is in fact strong evidence that insomnia is associated with medical and psychiatric illness and that the sleepiness associated with insomnia is the cause of many accidents. Thus, the direct (visits to doctors, cost of sleeping medication, complications from use of these medications) and indirect (accidents, quality of life) costs of insomnia are enormous and constitute a major public health problem in the industrialized countries. Believing that it is now timely to assess the state of this important research area, a consensus conference was convened on June 26-28, 1998, in Porto Cervo (Italy) to attempt to clarify the important issues and findings on the clinical effect of the different classes of antidepressant drugs on sleep quality in depression. The participants' consensus on some of the main topics is presented with the hope that this discussion and analysis will contribute to productive research in this important field.

Effect of zopiclone and temazepam on sleep EEG parameters, psychomotor and memory functions in healthy elderly volunteers.

RATIONALE: The increased prevalence of sleep disturbance in old age is accompanied by a higher prescription rate of hypnotics, predominantly benzodiazepines in the elderly. In young volunteers zopiclone exerts a beneficial effect on sleep continuity without suppression of SWS and REM sleep; psychomotor performance and vigilance seemed to be less impaired than under classical benzoediazepines. OBJECTIVE: The present study investigates the effects of zopiclone on sleep EEG and cognitive performance in comparison to temazepam and placebo in the elderly population. METHODS: Single oral doses of zopiclone (7.5 mg), temazepam (20 mg) and placebo were administered in a randomized double-blind, completely counterbalanced cross-over design to 12 healthy elderly men and women (65.9 +/- 3.6 years, range 60-70 years). On each of the 3 study nights a sleep EEG was registered from 10 p.m. to 6.30 a.m. and cognitive performance tests were applied at 8 p.m., 2 a.m. (when subjects were awake for 30 min), 7 a.m. and 9 a.m. RESULTS: After zopiclone treatment, sleep continuity had significantly improved and sleep stage 4 was increased compared to temazepam and placebo. In addition, both active substances significantly reduced REM density. Neither active compound substantially altered psychomotor and memory performance. CONCLUSIONS: Zopiclone and temazepam can be considered as effective hypnotics in elderly subjects when administered in that dosage. The superiority of zopiclone on sleep architecture may be related to a more specific action of zopiclone at the GABA-A benzodiazepine receptor complex. The suppression of REM density by both compounds and their subtle effects on cognition may reflect a GABAergic mediated reduction of cholinergic neuro-transmission.

[Phytotherapeutic drugs and sleep]. / Phytotherapeutika und Schlaf.

Most of the studies about phythotherapeutics and sleep confirmed only hypnotic effects on subjective sleep variables. For LI 160, a hypericum extract, an induction of slow wave sleep was demonstrated in older volunteers. In patients with major depression (MD) an increase of slow wave sleep was observed by our group after a six week therapy with hypericum extract (LI 160) and after an adjunct therapy with Ginkgo biloba LI 1370 extract. In MD sleep disturbances and hypersecretion of glucocorticoids are common features. For LI 160 beneficial effects on depressed mood and for LI 1370 effects on cognitive functioning are well documented. The potential relationship between influence on sleep structure and the hypothalamic-pituitary-adrenal axis will be discussed within the neurophysiological-neuroendocrine "extended two process model" of sleep regulation.

Sleep in depression and sleep deprivation: a brief conceptual review.

Risk factors for somnipathies are psychological stress or psychiatric illness. More severe sleep difficulties have been found to be clearly related to psychiatric illness such as depression and phobias, as well as to addiction. Somnipathies can objectively be identified by means of polygraphy. Overall, polysomnographic measures in patients with affective disorders differ most frequently and significantly from those in normal control subjects. Persistent sleep disturbances are associated with significant risk of both relapse and recurrence in mood disorders and an increased risk of suicide. In addition to changes in sleep architecture, patients with major depression show profoundly altered patterns of nocturnal hormone secretion, possibly through mechanisms that link regulation of sleep with neuroendocrine activity. Basic and clinical approaches of sleep research established neurobiological models into the underlying pathophysiology associated with psychiatric disorders.

[Clinical efficacy and tolerance of the hypericum special extract LI 160 in depressive disorders--a drug monitoring study]. / Wirksamkeit und Verträglichkeit des Hypericum-Spezialextraktes LI 160 bei depressiven Verstimmungen--eine ambulante Anwendungsbeobachtung.

PATIENTS AND METHODS: 647 patients suffering from mild to moderate depression treated for 6 weeks with hypericum extract LI 160 (Jarsin 300), 1 tablet t.i.d. RESULTS: The condition of the patients improved in 75% (primary endpoint). The von Zerssen depression score decreased from 19.8-21.2 (95%-CI) at base-line to 8.1-9.3 at week 6 (p < 0.001). All symptoms were improved at week 3 and further at week 6. The condition improved somewhat slower in patients older than 65 years. The severity of the depression did not appear to have an effect on the outcome. Adverse events were reported by 17% of the patients (gastrointestinal 10%). These were mostly mild or moderate. Tolerance was rated in 89% as satisfactory or better.

Contingent negative variation and attention in schizophrenic and depressed patients.

Contingent negative variation (CNV) is supposed to be a psychophysiological indicator of attention and arousal. Both have been reported to be deteriorated in schizophrenic and depressed patients. Thirty-four patients with major depression, 43 patients with schizophrenia and 49 healthy subjects were investigated during acute illness with a complex three-stimulus go/no-go task which requires different states of attention: trials consisted of three complex figures that were tachistoscopically presented. Three identical figures had to be confirmed by pressing a button (target condition). CNV was measured: (1) after the first figure waiting for the second (baseline condition), (2) after two identical figures waiting for the third (response-relevant condition), (3) after two different figures waiting for the third (response-irrelevant condition). The response-relevant condition compared to baseline significantly intensified CNV in healthy controls and to a minor extent in depressed patients but not in schizophrenics. In the response-relevant conditions in healthy controls, CNV was significantly reduced compared to the response-relevant condition. This clear discrimination between response-relevant and response-irrelevant conditions was not observed in either group of patients. Thus, the applied CNV paradigm was able to discriminate schizophrenic and depressed patients from healthy controls. Furthermore, subtle differences between schizophrenic and depressed patients were detected, reflected by the different CNV development across experimental conditions.

[Therapy refractory depression]. / Therapieresistente Depression.

Patients who fail in an adequate trial of a standard antidepressant drug (corresponding to 150 mg/d imipramine over a minimal period of 4 weeks) are defined as treatment resistant. According to these guidelines a substantial number of patients is not sufficiently treated and, thus, should be reassessed for dosage and length of antidepressant medications. If patients fail to a sufficient treatment a response may be achieved if they are switched to an alternative drug and/or if biochemically differently acting antidepressants are combined. Furthermore, an increasingly popular approach to handle treatment resistance is the use of augmentation strategies. Among these, lithium and thyroid T3 are the most well studied with the most consistently positive results. As non-pharmacological augmentation approach partial sleep deprivation has proved to be effective in combination with antidepressant medication. Finally, patients who had no or only a partial response to several treatments with antidepressants may benefit from electroconvulsive therapy.

Microsleep during partial sleep deprivation in depression.

BACKGROUND: Sleep deprivation (SD) exerts a beneficial effect on mood and sleep in about 60% of depressed patients usually followed by a relapse into depression after the recovery night. Short phases of sleepiness, especially naps in the early morning, may be responsible for this phenomenon. METHODS: To evaluate the effect of short, even ultrashort phases of sleep-microsleep (MS) during partial sleep deprivation (PSD) on mood, cognitive psychomotor performance (CPP), and sleep, an electroencephalograph (EEG) was continuously recorded over 60 hours in 12 patients with major depression. Subjective mood was assessed by a visual analogue scale and CPP by a letter cancellation test. RESULTS: The results illustrate that in depressed patients during PSD the amount of MS is increased, predominantly in the early morning, which was subjectively unrecognized and not observed by nursing staff. Patients with a low cumulative amount of MS during PSD improved significantly in mood, CPP, and sleep pattern compared to the patients with a high amount of MS who showed only slight changes. CONCLUSION: Therefore, accumulated MS may influence the SD-induced positive effects in depressed patients.

Effect of sleep deprivation on neuroendocrine response to a serotonergic probe in healthy male subjects.

Neuroendocrine responses to stimulation with a selective serotonin reuptake inhibitor (citalopram) were measured to investigate the effects of all-night sleep deprivation on serotonergic function in healthy male subjects (n = 7). We studied citalopram-stimulated prolactin and cortisol plasma concentrations in a placebo-controlled cross-over protocol following sleep and sleep deprivation. Citalopram infusion (20 mg i.v. at 14:20-14:50 h) after a night of undisturbed sleep prompted robust increases in both plasma prolactin and cortisol concentrations. Following a night of sleep deprivation, by contrast, the citalopram-induced prolactin response was blunted, but the cortisol response was not significantly altered. This differential response pattern relates to the distinct pathways through which serotonin may activate the corticotrophic and the lactotrophic systems. While an unchanged cortisol response does not indicate (but also does not refute the possibility of) an altered serotonergic responsivity following sleep deprivation, the suppressed prolactin response could reflect a downregulation of 5-HT1A or 2 receptors. An alternative, not mutually exclusive, explanation points to the possibility that sleep deprivation activates the tubuloinfundibular dopaminergic system, the final inhibitory pathway of prolactin regulation.