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Biomedical subjects

G Hajak

Publications and source records attributed to G Hajak.

At least 73 records · Page 4Linked to original sources
PubMed1998

Rebound insomnia after hypnotic withdrawal in insomniac outpatients.

The effect of abrupt medication withdrawal (no-pill discontinuation) was investigated in 1507 insomniacs using the patients' self-ratings on visual analogue scales. Drug discontinuation followed a 28-day treatment period with either 7.5 mg zopiclone, 0.25 mg triazolam, 1.0 mg flunitrazepam, or placebo in a randomized, double-blind, parallel group, multicenter study in private practice. Deterioration below individual pretreatment values (no-pill baseline) in at least one of three subjective parameters of sleep quality (sleep latency, total sleep time, nocturnal awakenings) and three parameters of daytime well-being (morning freshness, daytime tiredness, anxiety) were defined as rebound. The number of patients with rebound (rebound rate) was analyzed for every day of a 2-week posttreatment period. The overall rebound rate was higher in the placebo group (p < or = 0.001) than in each group treated with active drugs. Rebound rates affecting sleep quality were higher for placebo than for zopiclone (p < or = 0.001) and for flunitrazepam (p < or = 0.05). Rebound rates were smaller for zopiclone (p < or = 0.001) and flunitrazepam (p < or = 0.01) than for triazolam. Rebound in at least one item per day appeared in 21.5% (sleep quality) and 25.5% (daytime well-being) of the patients. Rebound decreased with increasing numbers of items of sleep quality or daytime well-being. Patients who did not respond to treatment showed higher rebound rates than those who were treatment responders (p < or = 0.001). Concerning treatment nonresponders, highest rebound was seen in the placebo group, whereas rebound was lowest in placebo responders. These results show that pill discontinuation itself may worsen sleep and daytime well-being in the sense of a rebound phenomenon. Furthermore, the number of patients with rebound remained at a high and varying level during the whole posttreatment period. This result indicates that a deterioration of sleep after drug withdrawal is not apparent during a few days but may last for longer periods in some patients and is modified by marked night-to-night variations.

Adolescent↗
PubMed1998

Safety and tolerance of zolpidem in the treatment of disturbed sleep: a post-marketing surveillance of 16944 cases.

The subjective response to treatment with zolpidem, an imidazopyridine hypnotic, was assessed in patients with insomnia under normal treatment conditions in an outpatients' practice in Germany. The uncontrolled clinical surveillance study included 16944 outpatients with subjective difficulties in initiating and/or maintaining sleep. Office-based neurologists, psychiatrists, internists and general practitioners were asked individually to adjust the dosage of zolpidem (age < or = 65 years, 10-20 mg; age > 65 years, 5-10 mg) over a recommended period of 3-4 weeks. In total, 82.8% of patients completed the survey (36% men, 64% women, mean age 58.8 +/- 14.9 years; 58.6% without previous hypnotic medication; duration of sleep complaints > 6 months in 40.6%, 1-6 months in 27.8%). Most patients (63.9%) took zolpidem on a daily basis. The average dose was 10 mg zolpidem per night in 74.8%, 5 mg in 19.8%, 20 mg in 2.4% and > 20 mg in 10 cases. Most physicians (87.6%) rated the efficacy of zolpidem as 'very good' or 'good'. One hundred and eighty-two (1.1%) of the 16 944 patients reported 268 adverse events (one adverse event in 113 cases, two adverse events in 53 cases and more than two adverse events in 16 cases). One hundred and eighteen (64.8%) of these patients (0.006% of all participating patients) discontinued treatment because of adverse events. Nausea (n = 36), dizziness (n = 35), malaise (n = 23), nightmares (n = 20), agitation (n = 19), and headache (n = 18) were the most common adverse events. There was one serious adverse reaction in a 48-year-old women who developed paranoid symptoms during the documentation phase. No life-threatening adverse event occurred. The adverse event profile reflected the pharmacological properties of zolpidem and underlined the cumulative good experience with the drug internationally.

Adolescent↗
PubMed1998

Altered circadian melatonin secretion patterns in relation to sleep in patients with chronic sleep-wake rhythm disorders.

Human well-being depends on the entrainment of endogenous circadian rhythms of biological functions and the sleep-wake rhythm. Although the incidence of otherwise healthy subjects with chronically altered sleep-wake rhythms is rather low, the investigation of these patients provides new sights into circadian entrainment mechanisms. We therefore examined the circadian rhythm of circulating melatonin and the sleep-wake rhythm in five patients with chronic sleep-wake rhythm disorders and ten age-matched healthy controls. All patients showed altered circadian melatonin rhythm parameters in relation to their sleep-wake cycle compared to age-matched controls. These alterations were random, i.e., independent of the type, the duration, and the age of onset of the disorder. The melatonin onset to sleep onset interval varied between the patients and the melatonin acrophase to sleep offset interval was prolonged in four patients. These findings indicate individual phase relations between the circadian melatonin rhythm and the sleep-wake cycle in patients with chronic sleep-wake rhythm disorders. Since the prolonged melatonin acrophase to sleep offset interval was the most consistent finding independent of aetiological origins, this abnormality may be one possible maintaining factor in chronic sleep-wake rhythm disorders due to reduced phase-resetting properties of the circadian pacemaker. Furthermore, rather low circadian melatonin amplitudes and a subsensitivity to daylight may maintain the disorder in at least some patients.

Adult↗
PubMed1997

Pergolide: treatment of choice in restless legs syndrome (RLS) and nocturnal myoclonus syndrome (NMS). A double-blind randomized crossover trial of pergolide versus L-Dopa.

A double-blind randomized crossover study of 0.125 mg Pergolide (Lilly) at bedtime versus 250mg L-Dopa + Carbidopa (Roche) was conducted in 16-day phases in 11 patients with idiopathic restless legs syndrome. Two patients reported a partial and 9 patients a complete relieve of motor restlessness while receiving Pergolide. Only 1 patient experienced an improvement of restlessness after L-Dopa. The patients showed polysomnographically a mean decrease in NMS cluster disturbed time by 45% from control on L-Dopa (p < 0.025) and by 79% from control on Pergolide (p < 0.001). In addition, Pergolide increased the total sleep time compared to L-Dopa (p < 0.05). In conclusion, the dopamine agonist Pergolide is superior to L-Dopa in the treatment of RLS and NMS.

Aged↗
PubMed1997

No evidence for a physiological coupling between melatonin and glucocorticoids.

Much has been speculated about the existence of a physiological coupling between melatonin and glucocorticoid secretion and about a possible anti-stress action of melatonin. We examined the relationship between melatonin and glucocorticoid secretion under close-to-physiological conditions, when the plasma concentration of either melatonin or glucocorticoids was elevated acutely or chronically in both rats and humans. Tryptophan administration caused a massive rise of plasma melatonin, but had no effect on corticosterone levels in rats or on cortisol levels in humans. The acute and long-lasting exposure of rats to uncontrollable stress resulted in a significant rise of adrenal corticosterone secretion, but had no effect on circulating melatonin levels. Orchectomy caused an initial increase in circulating corticosterone (when melatonin was unaffected) and a delayed rise in circulating melatonin (when corticosterone levels were normalized). In humans, no correlation was found between the nocturnal urinary excretion of melatonin and cortisol, either among healthy subjects, or among patients suffering from panic disorder (with an increased urinary excretion of cortisol) or among insomnia patients (with a high incidence of low melatonin secretion). Furthermore, no evidence was found for a suppressive action of melatonin on dexamethasone-mediated thymus regression in rats and on dexamethasone-mediated suppression of lymphocyte proliferation in vitro. Taken together, the results of this study provide no evidence for the existence of mutual influences between melatonin and glucocorticoid secretion, nor do they support the proposed attenuation of glucocorticoid-mediated effects on target cells or tissues by melatonin under physiological conditions.

Adult↗
PubMed1997

On the problems of switching from intravenous to oral administration in drug treatment of endogenous depression--a placebo-controlled double-blind trial with doxepin.

In the treatment of depressive disorders the onset of action can be accelerated if the antidepressant drug is initially administered by intravenous infusion. It is not clear whether this effect is due to pharmacological or to psychological effects of the infusion setting. The necessary switch to oral administration may be problematic. Uncontrolled observations indicate that it could be associated with a remarkable deterioration in the course of the disease. This randomized double-blind placebo-controlled study on doxepin is the first investigation of the effect of the switch from parenteral to oral administration on symptoms of endogenous depression. The hypothesis to be tested, that there is a significant worsening of treatment response during the switch, must be rejected on the basis of objective and subjective psychometric tests. There was in fact a continuous improvement. Precondition was a selection of patients with typical "endogenous" depressions and maintenance of at least constant plasma levels of the active antidepressants. In patients under the age of 65 years this can generally be achieved by switching in a ratio of 125 mg i.v. to 250 per os in the case of doxepin. Individual case studies indicated that a worsening in the patient's progress after switching was correlated with a decreasing plasma level of the active drug. Low plasma level already during the infusion period, insufficient response, and questionable compliance on oral medication were associated. Due to large interindividual differences of plasma levels by a factor of 10, measurements before and after switching are required.

Administration, Oral↗
PubMed1997

Urinary excretion of cortisol, norepinephrine, testosterone, and melatonin in panic disorder.

Nocturnal urinary cortisol, norepinephrine, epinephrine, testosterone, and melatonin secretion patterns were studied in male patients with DSM IV/ICD-10 panic disorder (n = 16) over two series of 5 consecutive nights each. Night-time urinary excretion of cortisol, norepinephrine, and epinephrine was significantly elevated in drug-free patients compared to normal individuals (n = 13). Measurements were repeated after 4 weeks, and the same differences were found again. There were high correlations between the first and the second series of measurements. Testosterone and melatonin levels did not differ between panic patients and controls.

Adult↗
PubMed1997

[Psychological, psychotherapeutic and other non-pharmacologic forms of therapy in treatment of insomnia. Position of the "Insomnia" Study Group of the German Society of Sleep Research and Sleep Medicine].

Psychological and psychotherapeutic techniques are an essential part of the treatment of insomnia. Mainly two facts stress the importance of psychological/psychotherapeutical strategies for insomnia: (1) Concepts for non-drug treatment aim at improvement of the symptoms and the underlying cause of the disease and (2) disadvantages of hypnotic therapy such as substance abuse or addiction are avoided. Effective treatment techniques such as patients education and counseling, sleep hygiene, stimulus control and relaxation techniques should be known to every therapist, especially general practitioners who treat the majority of patients haring difficulties in initiating or maintaining sleep. Several other effective behavioural techniques, e.g. sleep restriction, or cognitive therapy, and psychotherapy should be used only by skilled and trained experts. Insomniacs with chronic and severe complaints should be treated by therapists with experience in sleep medicine. Multimodal treatment strategies are provided for by sleep disorder centres and combine effective treatment elements in structured therapeutic concepts. There is absolute consensus of opinion that every hypnotic treatment of an insomniac patient should be combined with basal elements of non-drug treatment strategies.

Behavior Therapy↗
PubMed1997

[Value of sports in treatment of psychiatric illness].

Several studies in healthy volunteers have shown a positive effect of endurance training on anxiety, depressive symptoms, self-esteem, concentration and stress tolerance. There are only a few controlled studies examining the therapeutic potential of exercise in psychiatric disorders. However, there is good evidence that exercise is effective in mild to moderate depression and in anxiety disorders. The therapeutic effect did not correlate with changes in cardiopulmonary fitness in the majority of studies. Therefore, other neurobiological and psychological mechanisms are discussed which might explain the effectiveness of regular physical training. The authors offer a variety of suggestions, how exercise could be integrated and evaluated in the treatment of psychiatric disorders.

Anxiety Disorders↗
PubMed1996

[123I]IBZM SPET analysis of dopamine D2 receptor occupancy in narcoleptic patients in the course of treatment.

Elevated levels of central D2 dopamine receptors were found on postmortem examination in cases of human narcolepsy. In vivo investigations using positron emission tomography (PET) and single photon emission tomography (SPET) found no changes of D2 binding in the striatal structures. To investigate whether the elevated D2 receptors in postmortem investigations are due to long-term treatment effects, we applied 123I-labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) ([123I]IBZM, a highly selective CNS D2 dopamine receptor ligand) and SPET in narcoleptic patients in the course of treatment with stimulants and/or antidepressants. Before treatment we found no changes in D2 binding in 10 patients (in comparison to 10 normal controls). After treatment (performed in five patients for 3 months) we found changes in D2 binding in four of them, indicating that the results of the postmortem studies could have been influenced by long-term medications. Human narcolepsy seems not to be related to a striatal D2 dopaminergic disturbance.

Adolescent↗
PubMed1996

Lamotrigine in the treatment of nocturnal myoclonus syndrome (NMS): two case reports.

In previous investigations we found an increase of D2 dopamine receptors in the striatum of patients with nocturnal myoclonus syndrome (NMS) after treatment with dopamimetics. Under the hypothesis, that, according to animal experiments, the glutamatergic system could be involved in this atypical dopaminergic up-regulation in NMS. The glutamate release inhibitor lamotrigine was tested in up to now two NMS patients. The results and the success of this approach and its implications are discussed.

Anticonvulsants↗
PubMed1996

Effects of chronic treatment with methadone and naltrexone on sleep in addicts.

Previous studies have described sleep disturbance secondary to chronic opiate use and abuse. Drug-dependency insomnia is of interest because chronic sleep disturbances can promote depressive symptoms which could lead to a drug relapse. For the first time we compared the polysomnographic parameters of 10 methadone-substituted outpatients and 10 naltrexone-treated outpatients. Methadone (mu-opioid agonist) produced a marked fragmentation of the sleep architecture with frequent awakenings and a decrease in EEG arousals. In comparison with methadone and controls, the naltrexone (mu-opioid antagonist) group showed the shortest sleep latency and the longest total sleep time. These data indicate that mu-agonists and mu-antagonists have different effects on sleep. The implications, especially the involvement of opioid-dopamine interactions on sleep and movements during sleep, are discussed.

Adult↗
PubMed1996

Rebound insomnia after abrupt clozapine withdrawal.

Rebound insomnia has been reported upon discontinuation of benzodiazepines. We describe the first case of a sleep polygraphically documented rebound insomnia with an unusual somatic fatigue syndrome after long-term use of clozapine in a 30-year-old schizophrenic male. The withdrawal symptoms occurred the first day after drug discontinuation and could be stopped by readministering clozapine. In our opinion, the sudden occurrence of the withdrawal symptoms cannot be explained by a dopaminergic hypersensitivity or a cholinergic rebound, but indicates an involvement of GABAergic and perhaps antiglutamatergic properties of clozapine.

Adult↗
PubMed1996

[Ambulatory, comprehensive, behavior therapy-oriented weight reduction program (Optifast Program). An alternative therapy in obstructive sleep apnea].

We investigated the therapeutic effect of marked body weight reduction on the predominantly obstructive sleep apnea syndrome by the application of an out-patient, behaviour therapy based body weight reduction program (Optifast-program) in five of our obese apnea patients (mean overweight by Broca 53.6 +/- 24.8 kg). Mean body weight reduction was 32.7 +/- 15.8 kg after six months. The mean apnea-index of 34.5 +/- 23.1/h prior to the weight reduction dropped to 7.8 +/- 6.1/h after therapy. The mean apnea-hypopnea-index (so called "respiratory disturbance index", RDI) could be reduced from 45,7 +/- 26.0/h to 14.0 +/- 11.4/h. The best therapeutic effect on the sleep related respiratory parameters was seen in patients who reached their normal weight whereas the absolute weight reduction itself seems to be less important. Our results should encourage this causal therapy in appropriate patients.

Adult↗
PubMed1996

Nocturnal plasma melatonin levels after flunitrazepam administration in healthy subjects.

Polysomnographic sleep patterns and melatonin secretion were investigated in 5 young (age 25.6 +/- 1.1 years) and 5 middle-aged (age 49.4 +/- 5.4 years) healthy male subjects after intravenous administration of 1 mg flunitrazepam and placebo in a randomized, double-blind and cross-over setting. The area under the curve (AUC) of total nocturnal melatonin plasma concentration decreased 23.3 +/- 11.5% in young subjects (P < or = 0.05) and 39.3 +/- 5.2% in middle-aged subjects (P < or = 0.05) after flunitrazepam infusion compared with placebo infusion. Differences in nocturnal peak values of melatonin were 5.4 +/- 22.0% in young subjects (not significant) and 34.0 +/- 14.7% in middle-aged subjects (p < or = 0.05). Flunitrazepam significantly (P < or = 0.05) improved sleep latency and the number of sleep stage changes in the group of all subjects. These results show that, although the benzodiazepine flunitrazepam improves sleep, it reduces the nocturnal secretion of melatonin, and therefore alters the circadian rhythm of a hormone which is supposed to play a special role in circadian sleep-wake rhythmicity.

Adult↗
PubMed1996

Serotonin transporters in the rat frontal cortex: lack of circadian rhythmicity but down-regulation by food restriction.

Molecular biological findings have indicated that the affinity and the density of presynaptic serotonin transporters may be subject to adaptive regulation, but the physiological conditions that may act to trigger such changes are presently unknown. By means of [3H]paroxetine binding to rat cortical membranes, we studied the influence of two physiological variables that are clearly associated with altered serotonergic activity--circadian rhythm and semistarvation--on K(D)and Bmax values of the serotonin transporter of the rat frontal cortex. No circadian fluctuations of both parameters were observed. Also, semistarvation (50% reduction of normal voluntary food intake) for 2 days had no effect on either K(D) or Bmax values of cortical [3H]paroxetine binding. Food restriction for either 7 days or 2 weeks, however, resulted in a significant, approximately 30%, reduction of the density of cortical serotonin transporters with unchanged transporter affinity. These findings indicate that long-term changes in the density of cortical serotonin transporters can be induced by long-lasting alterations of certain environmental variables. Because the duration and the radius of action of presynaptically released serotonin are governed by the efficiency of the reuptake mechanism, such adaptive changes of serotonin transporter density must be expected to cause long-term alterations of the modulatory impact of the central serotonin system on certain brain functions.

Animals↗
PubMed1996

Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia.

Nocturnal melatonin secretion and polysomnographic sleep patterns were investigated in ten patients with chronic primary insomnia (age 41.3 +/- 9.5 years) and in five healthy subject, (age 27.2 +/- 0.7 years) after either a single intravenous administration of 25 mg doxepin or placebo in a randomized, double blind, and cross-over setting. In the patient group a third session was performed after a three-week open oral treatment with 25 mg doxepin daily. The single-dose administration of doxepin did not affect plasma melatonin concentrations in either the patients on the healthy subjects. After three weeks of oral doxepin intake by the patients, the area under the curve of total nocturnal plasma melatonin concentration was significantly increased by 26% and the peak values were increased by 30%. Both after the single i.v. treatment as well as after long-term oral administration, doxepin also significantly improved sleep latency, total sleep time, and sleep efficiency in the insomniacs as well as the healthy subjects, whereas the nocturnal wake time was decreased. These findings indicate that this tricyclic antidepressant not only improves sleep and but also preserves the secretion of a hormone which is believed to play a special role in the circadian sleep-wake rhythm. Long-term doxepin treatment of chronic insomniac patients not only improves sleep but also restores nocturnal melatonin secretion in these patients.

Adult↗