Insomnia in primary care.
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Chronic Disease↗
Biomedical subjects
G Hajak
Publications and source records attributed to G Hajak.
Salivary, total plasma and plasma free cortisol in panic disorder.
BACKGROUND: Research on basal HPA axis activity in patients with panic disorder showed inconsistent results. METHODS: Basal total plasma, plasma free and salivary cortisol levels were compared in patients with panic disorder (n = 47) and in healthy individuals (n = 23). Correlations between these fractions were calculated. RESULTS: All three basal cortisol fractions were significantly elevated in patients compared to controls. There were significant correlations between all three cortisol fractions. CONCLUSIONS: Nonsignificant differences between cortisol levels of patients and healthy controls in previous studies may have been due to inclusion of less severely ill patients or to small sample sizes (96 words).
Adult↗
Risperidone in disorganised schizophrenia.
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Adult↗
Increased psychological responses and divergent neuroendocrine responses to m-CPP and ipsapirone in patients with panic disorder.
In patients with panic disorder and /or agoraphobia (PDA) an increased sensitivity of central 5-HT2C receptors and a decreased responsiveness of 5-HT1A receptors has been postulated. In the present study, neuroendocrine challenges were performed using oral doses of the non-selective 5-HT2C agonist m-chlorophenylpiperazine (m-CPP) (0.4 mg/kg), the selective 5-HT1A antagonist ipsapirone (0.3 mg/kg), and placebo in 40 patients with PDA and 12 healthy controls in order to compare 5-HT2C and 5-HT1A-specific psychobehavioural and neuroendocrine response patterns. At baseline, all psychobehavioural variables and the plasma concentration of noradrenaline (NE) were significantly increased in the patient group compared to the controls. The administration of m-CPP or ipsapirone was followed by comparable psychological symptoms and, in 55% of all patients, panic attacks. In comparison to the control subjects, patients were characterized by significantly higher psychological reactions to both challenge agents and a significantly higher NE response to m-CPP. In the patient group, there was also a trend towards an increased cortisol response after administration of m-CPP and a decreased cortisol and hypothermia response after administration of ipsapirone compared to the control group. The neuroendocrine findings of our study support earlier reports of opposite changes in the responsiveness of 5-HT2C and 5-HT1A-related receptors in PDA patients. The behavioural hypersensitivity to both, m-CPP and ipsapiron, shows that the provocation of anxiety and other psychological symptoms might be influenced by
Adolescent↗
Salivary cortisol in panic attacks.
OBJECTIVE: Documentation of hypothalamic-pituitary-adrenal (HPA) axis disturbance in panic disorder has been inconsistent. Increased cortisol levels have been associated with altered HPA function due to stress. The authors examined salivary cortisol levels in spontaneously occurring, unprovoked panic attacks. METHOD: Patients with panic disorder (N=25) collected saliva samples when panic attacks occurred. Levels of cortisol in the saliva samples were determined and were compared with levels in comparison samples of saliva obtained 24 hours after the panic attack occurred. RESULTS: During spontaneous panic attacks there was a subtle but significant elevation of cortisol levels, compared with levels obtained 24 hours later. No significant correlations were found between the cortisol elevations during panic attacks and the severity of the attack as measured by using the Acute Panic Inventory or the severity of illness as measured by using the Panic and Agoraphobia Scale. CONCLUSIONS: Saliva sampling may be a useful method for investigating neuroendocrine parameters during spontaneously occurring panic attacks.
Adult↗
Clozapine in the treatment of mania.
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Adult↗
Nocturnal melatonin secretion and its modification by treatment in patients with sleep disorders.
Data on the circadian melatonin secretion in sleep disordered patients and effects of sleep medication on melatonin are still missing. We studied plasma melatonin concentration, sleep, and effects of some hypnotics in 15 patients and 10 controls. Nocturnal melatonin levels were significantly decreased in patients with a more than five years history of sleep complaints compared to controls or patients with a shorter duration of illness. Independent of their sleep promoting properties drugs increased or decreased nocturnal melatonin in controls and patients. Patients with chronic sleep-wake rhythm disorders showed altered relations between their circadian melatonin secretion pattern and sleep. We conclude that nocturnal melatonin secretion is primarily independent of sleep regulation but represents a neuroendocrine feature of chronically disturbed sleep.
Adult↗
Sleep disorders and portal-systemic encephalopathy following transjugular intrahepatic portosystemic stent shunt in patients with liver cirrhosis. Relation to plasma tryptophan.
Neuropsychiatric symptoms due to any type of dysfunction and/or portal-systemic shunting are summarized as hepatic encephalopathy (HE). HE in the presence of liver cirrhosis and/or portal-systemic shunting has been termed portal-systemic encephalopathy (PSE). PSE is most frequent among the HE syndromes and is almost exclusively seen in patients with advanced cirrhosis and portal hypertension. Portal-systemic shunting either spontaneous due to portal hypertension, following surgical portocaval anastomosis, or subsequent to transjugular intrahepatic portosystemic stent-shunt (TIPSS) is regarded as the primary causative condition for PSE, not hepatic dysfunction per se. PSE may be considered as a disorder of multiple neurotransmitter systems among which derangements of the serotonergic system have been documented most consistently. Incipient PSE is frequently paralleled by the occurrence of sleep disorders, however, their relation to PSE remains unclear. We observed a transient increase of sleep disorders post-TIPSS, which were only in part correlated to other symptoms of PSE. Among the biochemical parameters studied only an association between arterial ammonia levels and sleep disorders became apparent, whereas no significant relation was observed for peripheral tryptophan.
Adult↗
Application of a new statistical approach to evaluate a clinical trial with panic disorder patients.
In clinical trials in psychiatry, changes in severity are usually measured with ordinal level scales which are applied repeatedly during the trial, showing a constant decline in psychopathology scores as treatment leads to improvement. Previous non-parametric tests for repeated measures in factorial designs did not test the hypothesis that scale scores decrease constantly during the trial. A recently developed "rank test for ordered alternatives in a mixed model" was developed and applied to the data of a clinical trial in panic disorder. Thirty-seven outpatients with panic disorder and agoraphobia (PDA) were treated with imipramine (75-150 mg/day) in an 8-week open, prospective trial. Patients with intercurrent agoraphobia were instructed in practising self-exposure in their agoraphobic situations. The total score on the Panic and Agoraphobia Scale, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy measures. The new rank test showed significant treatment results in all scales applied. Treatment results were excellent, as was shown by a decrease in the average Panic and Agoraphobia Scale severity scores from 28.9 (range 14-45) to 13.3 (range 0-37; rank statistic Tn = 6.7; p < 0.0001). The largest effect size r(w) of all clinician-rated scales was seen with the observer-rated version of the Panic and Agoraphobia Scale, although closely followed by the CGI and the HAMA. Among the self-rated scales, the Panic and Agoraphobia Scale also showed the largest effect size. All five subscores of the Panic and Agoraphobia Scale showed significant improvements. The highest treatment effect sizes were seen in the "panic attacks" subscore, followed by the "anticipatory anxiety" subscore. The new statistical test applied in this study, which has some advantages in comparison with previously applied tests, is suitable for psychiatric treatment evaluations since it can also be applied in the case of discrete repeated measurements.
Adult↗
Decreased neuroendocrine responses to meta-chlorophenylpiperazine (m-CPP) but normal responses to ipsapirone in marathon runners.
Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise. To study the effects of exercise on central serotonergic receptor sensitivity, we performed neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP, 0.4 mg/kg), ipsapirone (0.3 mg/kg) and placebo in 12 marathon runners and 12 healthy controls not practicing regular exercise. After administration of the nonselective serotonergic agonist m-CPP, which exerts a number of well-reproducible effects mainly by means of its action on 5-HT2C receptors, marathon runners showed a significantly reduced cortisol response in comparison to the control group. There was also a statistical trend toward a blunted prolactin response after m-CPP in the athlete group. In contrast, the increase of cortisol and the hypothermia observed after administration of the 5-HT1A agonist ipsapirone were of the same magnitude in both groups. The behavioral response to m-CPP or ipsapirone and the mean maximal increases of plasma adrenaline and noradrenaline did not differ between the marathon and the control group. In conclusion, exercise-induced downregulation of 5-HT2C receptors could play an important role in mediating the anxiolytic and antidepressive effects of exercise.
Adult↗
Influence of acetazolamide and CO2 on extracranial flow volume and intracranial blood flow velocity.
BACKGROUND AND PURPOSE: The vasomotor response can be tested by means of transcranial Doppler sonography. If a constant vessel diameter is assumed, the flow velocity changes will reflect blood flow volume changes. This hypothesis is difficult to verify. Simultaneous assessment of intracranial flow velocity and extracranial flow volume changes may solve this problem. METHODS: We tested vasomotor response in 32 volunteers (age, 42+/-18 years) with 5% CO2. Acetazolamide (1 g) was tested in 15 volunteers (age, 28+/-8 years). To evaluate drug-dependent flow changes in the external carotid artery territory, acetazolamide was administered in 7 patients with unilateral occlusion of the internal carotid artery without evidence of collateralization through the ophthalmic artery (age, 67+/-12 years). Simultaneous recording included measurements of flow volume in the common carotid arteries (M-mode color duplex system) and flow velocity in the middle cerebral arteries. RESULTS: With CO2 and acetazolamide, intracranial flow velocity increased by 31% and 39%, respectively, with a simultaneous increase of common carotid artery flow volume of 47% and 50%, respectively. No change in extracranial flow volume was observed in patients with an occluded internal carotid artery. CONCLUSIONS: These data show not only the expected increase of flow velocity in the middle cerebral artery but also suggest an increase in cross-sectional vessel diameter of 6% and 4% with CO2 and acetazolamide, respectively. It remains unresolved whether this observation is due to a direct effect of the drug on the vessel walls or is simply pressure dependent.
Acetazolamide↗
Evaluation of severe insomnia in the general population: results of a European multinational survey.
The epidemiology of severe insomnia and its effect on quality of life and healthcare consumption was assessed in a survey of the general population of five northern European countries. Applying established consumer sampling techniques, insomnia sufferers were selected from the general population using a questionnaire, conducted by face-to-face interview, and severity of insomnia was ranked (severe, mild/moderate, no sleep complaint) using a specific algorithm. Population samples were matched according to case control methodology for age, gender and geographical region. A second questionnaire gathered information on sleep problems, quality of life (SF-36 scores) and healthcare consumption. The prevalence of severe insomnia ranged from 4% to 22%, was higher in females than in males, but did not increase significantly with age. Patients with severe insomnia had been experiencing sleeping problems for a median of 2-6 years. In all countries, insomnia had a negative impact on quality of life, and the degree of impairment in quality of life was directly related to the severity of insomnia. Individuals with severe insomnia also showed a higher level of healthcare consumption. Despite this, severe insomnia did not appear to feature prominently in the doctor-patient relationship.
Adult↗
Evaluation of severe insomnia in the general population--implications for the management of insomnia: the German perspective.
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Algorithms↗
A comparative assessment of the risks and benefits of zopiclone: a review of 15 years' clinical experience.
Zopiclone is a cyclopyrrolone hypnosedative that is chemically unrelated to the benzodiazepines but nevertheless potentiates gamma-aminobutyric acid-mediated neuronal inhibition, and has demonstrated proven efficacy and good tolerability in the treatment of insomnia over 15 years of use. Zopiclone is indicated for short term use, and should not be prescribed for more than 4 weeks. This review compares the efficacy of zopiclone with that of a number of commonly used short-, medium- and long-acting benzodiazepines. Zopiclone at dosages of 7.5 mg/day has demonstrated efficacy equivalent and in some cases greater to that of flurazepam 30 mg/day, nitrazepam 5 mg/day, flunitrazepam 1 to 2 mg/day, temazepam 20 mg/day, triazolam 0.125 to 0.5 mg/day and midazolam 15 mg/day. Zopiclone-treated patients reported themselves to be less impaired by daytime sedation than patients treated with the medium- and long-acting hypnosedatives flurazepam, nitrazepam and flunitrazepam. Zopiclone and temazepam showed similar effects on daytime behaviour while zopiclone appeared to have somewhat better effects on daytime well-being than the short-acting triazolam and midazolam. There has been no clinical comparison with the frequently used medium-acting benzodiazepines lormetazepam and brotizolam and the imidazopyridine hypnosedative zolpidem. Data from clinical trials, pooled analyses and postmarketing surveillance including over 30,000 patients showed that with the exception of bitter taste (reported by <10% of zopiclone recipients), the tolerability profile of zopiclone is similar to that of placebo. Clinical trials found no evidence for significant rebound insomnia and indicated that the risk of withdrawal reactions with therapeutic doses of zopiclone is very low. In addition, to date, dependency appears very low, although abuse potential should be considered following a history of addiction or psychiatric illness. Evaluation of the accumulated evidence from over 2.5 billion units dispensed in more than 30 countries indicates that zopiclone is effective, well tolerated and an excellent alternative to benzodiazepines in the short term treatment of insomnia.
Animals↗
First results on daytime submandibular electrostimulation of suprahyoidal muscles to prevent night-time hypopharyngeal collapse in obstructive sleep apnea syndrome.
Daytime submandibular electrostimulation (dSE) of suprahyoidal muscles was applied to prevent sleep-associated collapse of the tongue into the hypopharyngeal airway. By placing the stimulatory electrodes intra- and extraorally, recruitment of stimulated muscle fibers at low current densities was improved. The significant impact of electrostimulation on suprahyoidal muscle force was initially demonstrated in healthy controls as compared to placebo-treated volunteers. The morphology of suprahyoidal muscles was not affected by this treatment. A patient with obstructive sleep apnea syndrome initially presented with a respiratory disturbance index (RDI) of 13.2, an oxygen desaturation index of 23 and a minimal oxygen saturation of 75%. After two weeks of placebo treatment (TENS-stimulation), respiratory parameters remained unchanged. Two weeks of dSE treatment, however, improved the RDI to 3.9, the oxygen desaturation index from 23 to 2.8 and the minimal oxygen saturation from 75% to 88%. 3D-sonography showed considerable hypertrophy of the stimulated muscles. These results indicate that dSE may prevent episodes of apnea induced by sleep-associated hypopharyngeal collapse of the tongue.
Adult↗
Sleep and rTMS. Investigating the link between transcranial magnetic stimulation, sleep, and depression.
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Affect↗
High-frequency repetitive transcranial magnetic stimulation delays rapid eye movement sleep.
Repetitive transcranial magnetic stimulation (rTMS) is a promising new treatment for patients with major depression. However, the mechanisms underlying the antidepressive action of rTMS are widely unclear. Rapid eye movement (REM) sleep has been shown to play an important role in the pathophysiology of depression. In the present study we demonstrate that rTMS delays the first REM sleep epoch on average by 17 min (102.6 +/-22.5 min vs 85.7+/-18.8 min; p < 0.02) and prolongs the nonREM-REM cycle length (109.1+/-11.4 min vs 101.8+/-13.2min, p< 0.012). These rTMS-induced changes in REM sleep variables correspond to findings observed after pharmacological and electroconvulsive treatment of depression. Therefore, it is likely that the capability of rTMS to affect circadian and ultradian biological rhythms contributes to its antidepressive action.
Adult↗
The use of the Panic and Agoraphobia Scale in a clinical trial.
A new scale for assessing severity in PDA (Panic Disorder with/without Agoraphobia) has recently been developed: the Panic and Agoraphobia Scale [P & A (Bandelow, 1995)]. The objective of this study was to test whether the scale is sensitive to changes during a treatment trial. Thirty-seven patients (mean age, 32.7; S.D., 6.3) with PDA were treated with imipramine (75-150 mg/day) for 8 weeks in an open prospective trial. Patients with concurrent agoraphobia were instructed in practising self-exposure to agoraphobic situations. The total scores on the P & A, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy criteria. Treatment results were excellent, as could be shown by a decrease in the average severity scores of the P & A observer-rated version from 28.9 (S.D., 8.1) to 13.3 (S.D., 11.8; rank statistic T(N) = 6.7; P < 0.0001). The largest effect size r(w) of all clinician-rated scales was seen with the observer-rated version of the P & A, although closely followed by the CGI and the HAMA. Among the self-rated scales, the P & A (self-rated version) also showed the largest effect size. All five subscores of the P & A showed significant improvements. The highest treatment effect sizes could be seen in the 'panic attacks' subscore, followed by the 'anticipatory anxiety' subscore. The new Panic and Agoraphobia Scale (P & A) is a useful tool for measuring treatment efficacy in panic disorder trials.
Adult↗