Migraine with and without aura: association with depression and anxiety disorder in a population-based study. The HUNT Study.

Some data indicate that migraine with aura (MA) is more strongly associated with anxiety disorder and depression than migraine without aura (MoA), but the evidence is not conclusive. In the Nord-Trøndelag Health study 1995-1997, a total of 49 205 (75% of the participants) subjects gave valid answers to both HADS (Hospital Anxiety and Depression Scale) and a validated headache questionnaire. Associations between anxiety disorder/depression and MA/MoA were evaluated by multiple logistic regression analysis. Depression (DEP) [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.2, 2.6] and depression with comorbid anxiety disorder (COM) (OR 1.6; 95% CI 1.2, 2.1) were more likely in women having MA than in those with MoA. No stronger association was found for pure anxiety disorder (ANX) in MA vs. MoA (OR 0.9; 95% CI 0.7, 1.5). Among men, we found no difference in prevalence of depression and anxiety disorders between MA and MoA. This is a new finding that might have relevance for both research and clinical treatment.

Changes in neuronal conductance during different components of cortically generated spike-wave seizures.

Neuronal conductance was studied in anesthetized cats during cortically generated spike-wave seizures arising from slow sleep oscillation. Single and dual intracellular recordings from neocortical neurons were used. The changes were similar whether the seizures occurred spontaneously, or were evoked by electrical stimulation or induced by bicuculline. In all seizures, the conductance increased from the very onset of the seizure and returned to control values only at the end of the postictal depression. Simultaneous intracellular recordings from two neurons showed that the neuron leading the other neuron displayed the largest increase in membrane conductance. The changes in neuronal conductance during the two phases of the slow sleep oscillation, i.e. highest during depolarizations and lowest during hyperpolarizations, were similar to those occurring during the "spike" and "wave" components of seizures. (1) Maximal conductance was found during the paroxysmal depolarizing shift corresponding to the electroencephalogram "spike" (median: 252 nS; range: 90 to more than 400 nS). It was highest at the onset of the depolarized plateau and decreased thereafter. (2) During the hyperpolarization corresponding to the electroencephalogram "wave", the conductance was significantly lower (median: 71 nS; range: 41 to 140 nS). (3) The conductance was elevated during the fast runs (median: 230 nS; range: 92 to 350 nS) which occurred in two-thirds of the seizures. (4) The conductance values during postictal depression were situated between those measured during the seizure hyperpolarizations and during sleep hyperpolarizations. The conductance decreased exponentially back to the values of the slow sleep oscillation over the total duration of the postictal depression. The data suggest that the major mechanism underlying the "wave"-related hyperpolarizing component of spike-wave seizures relies mainly not on active inhibition, but on a mixture of disfacilitation and potassium currents.

Membrane capacitance of cortical neurons and glia during sleep oscillations and spike-wave seizures.

Dual intracellular recordings in vivo were used to disclose relationships between cortical neurons and glia during spontaneous slow (<1 Hz) sleep oscillations and spike-wave (SW) seizures in cat. Glial cells displayed a slow membrane potential oscillation (<1 Hz), in close synchrony with cortical neurons. In glia, each cycle of this oscillation was made of a round depolarizing potential of 1.5-3 mV. The depolarizing slope corresponded to a steady depolarization and sustained synaptic activity in neurons (duration, 0.5-0.8 s). The repolarization of the glial membrane (duration, 0.5-0.8 s) coincided with neuronal hyperpolarization, associated with disfacilitation, and suppressed synaptic activity in cortical networks. SW seizures in glial cells displayed phasic events, synchronized with neuronal paroxysmal potentials, superimposed on a plateau of depolarization, that lasted for the duration of the seizure. Measurements of the neuronal membrane capacitance during slow oscillating patterns showed small fluctuations around the resting values in relation to the phases of the slow oscillation. In contrast, the glial capacitance displayed a small-amplitude oscillation of 1-2 Hz, independent of phasic sleep and seizure activity. Additionally, in both cell types, SW seizures were associated with a modulatory, slower oscillation ( approximately 0.2 Hz) and a persistent increase of capacitance, developing in parallel with the progression of the seizure. These capacitance variations were dependent on the severity of the seizure and the distance between the presumed seizure focus and the recording site. We suggest that the capacitance variations may reflect changes in the membrane surface area (swelling) and/or of the interglial communication via gap junctions, which may affect the synchronization and propagation of paroxysmal activities.

Spike-wave complexes and fast components of cortically generated seizures. III. Synchronizing mechanisms.

The intracortical and thalamocortical synchronization of spontaneously occurring or bicuculline-induced seizures, consisting of spike-wave (SW) or polyspike-wave (PSW) complexes at 2-3 Hz and fast runs at 10-15 Hz, was investigated in cats under ketamine-xylazine anesthesia. We used single and dual simultaneous intracellular recordings from cortical areas 5 and 7, and extracellular recordings of unit firing and field potentials from neocortical areas 5, 7, 17, 18, as well as related thalamic nuclei. The evolution of time delays between paroxysmal depolarizing events in single neurons or neuronal pools recorded from adjacent and distant sites was analyzed by using 1) sequential cross-correlations between field potentials, 2) averaged activities triggered by the spiky component of cortical SW/PSW complexes, and 3) time histograms between neuronal discharges. In all instances, the paroxysmal activities recorded from the dorsal thalamus lagged the onset of seizures in neocortex. The time lags between simultaneously impaled cortical neurons were significantly smaller during SW complexes than during the prior epochs of slow oscillation. During seizures, as during the slow oscillation, the intracortical synchrony was reduced with increased distance between different cortical sites. Dual intracellular recordings showed that, during the same seizure, time lags were not constant and, instead, reflected alternating precession of the recorded foci. After transection between areas 5 and 7, the intracortical synchrony was lost, but corticothalamocortical volleys could partially restore seizure synchrony. These data show that the neocortex leads the thalamus during SW/PSW seizures, that time lags between cortical foci are not static, and that thalamus may assist synchronization of SW/PSW seizures after disconnection of intracortical synaptic linkages.

Spike-wave complexes and fast components of cortically generated seizures. II. Extra- and intracellular patterns.

In the previous paper we have demonstrated, by means of field potential and extracellular unit recordings, that bicuculline-induced seizures, which include spike-wave (SW) or polyspike-wave (PSW) complexes, are initiated intracortically and survive ipsilateral thalamectomy. Here, we used multisite field potential and extracellular recordings to validate the patterns of cortical SW/PSW seizures in chronically implanted, behaving cats. To investigate the cellular patterns and excitability during spontaneously occurring and electrically elicited cortical seizures, we used single and dual intracellular recordings from regular-spiking (RS) and fast-rhythmic-bursting (FRB) cortical neurons, in conjunction with field potential recordings from neocortex and related thalamic nuclei, in cats maintained under ketamine-xylazine anesthesia. 1) Invariably, the spontaneous or electrically induced seizures were initiated within the cortex of both behaving and anesthetized animals. Spontaneously occurring, compound seizures consisting of SW/PSW complexes at 2-4 Hz and fast runs at 10-15 Hz, developed without discontinuity from the slow (mainly 0.5-0.9 Hz), sleeplike, cortically generated oscillation. 2) During SW/PSW complexes, RS neurons discharged spike trains during the depth-negative component of the cortical "spike" component of field potentials and were hyperpolarized during the depth-positive field wave. The FRB neurons fired many more action potentials than RS cells during SW/PSW complexes. Averaged activities triggered by the spiky field potentials or by the steepest slope of depolarization in cortical neurons demonstrated similar relations between intracellular activities and field potentials during sleep and seizure epochs, the latter-being an exaggeration of the depolarizing and hyperpolarizing components of the slow sleep oscillation. 3) During the fast runs, RS cells were tonically depolarized and discharged single action potentials or spike doublets (usually with pronounced spike inactivation), whereas FRB cells discharged rhythmic spike bursts, time locked with the depth-negative field potentials. 4) Neuronal excitability, tested by depolarizing current pulses applied throughout the seizures and compared with pre- and postseizure epochs, showed a decreased number of evoked action potentials during both seizure components (SW/PSW complexes and fast runs), eventually leading to null responses during the postictal depression. 5) Data suggest that interconnected FRB neurons may play an important role in the initiation of cortical seizures. We discuss the similarities between the electrographic patterns described in this study and those found in different forms of clinical seizures.

Instrumental conditioning of fast (20- to 50-Hz) oscillations in corticothalamic networks.

Cats were instrumentally conditioned to generate grouped fast (20- to 50-Hz) oscillations in motor cortex (area 4). Over seven experimental sessions, there was a spatially selective increased generation of grouped fast oscillations in that electroencephalogram lead. This locally increased generation of fast oscillations in cortex was associated with a widespread increase in synchrony of fast oscillations in thalamocortical networks, as demonstrated by cross-correlations between intracortical, corticothalamic, and intrathalamic field potentials. A three-session extinction period abolished the local increase in generation of grouped fast oscillations and reset the thalamocortical synchrony of fast oscillations to control values. A subsequent series of seven sessions with instrumental conditioning of fast oscillations in visual cortex (area 17) reproduced the results from area 4, with a spatially selective increased generation of grouped fast oscillations in the criterion lead, associated with a widespread increase in thalamocortical synchrony of fast oscillations. In addition to their presence during the conditioning sessions, the changes in synchrony of fast oscillations were expressed during periods of quiet waking, rapid-eye-movement sleep, and nonrapid-eye-movement sleep recorded during the first hour after the end of the conditioning.

Hypothermia and the 5-HT syndrome induced by CGS 12066B independently of 5-HT(1B) receptor activation.

The effects of CGS 12066B (3-14mg/kg), a putative 5-HT(1B) agonist, on 5-HT behavioral syndrome, motor activity and body temperature, were investigated in rats. The animals were well adapted to the experimental conditions before testing, and data sampling started at the same hour for each rat. The highest dose of CGS 12066B clearly reduced body temperature and induced flat body posture and hindlimb abduction. No significant change was seen in motor activity. The CGS 12066B-induced changes were not antagonized by 5-HT(1B) receptor antagonists, or antagonists at other 5-HT receptor. In fact, the 5-HT(1A) antagonist NAN-190 and especially the non-selective 5-HT antagonist methiothepin, with definite 5-HT(1B) receptor blocking properties, both potentiated the decrease in body temperature. The findings suggest that the behavioral and body temperature effects of CGS 12066B are not easily explained by 5-HT(1B) receptor stimulation, but may be mediated by activation of non-serotonergic mechanisms. Similar conclusions in studies with other 5-HT(1B) agonists suggest a common problem with such drugs.

Citalopram: differential sleep/wake and EEG power spectrum effects after single dose and chronic administration.

The sleep/wake effects of the selective serotonin re-uptake inhibitor citalopram were studied in both a single-dose study with three dose levels (0.5, 2.0 and 5.0 mg/kg), and a 5-week chronic administration study (15 mg/kg/24 h). Single doses of citalopram resulted in a dose-dependent inhibition of rapid eye movement (REM) sleep. After chronic citalopram treatment there was a sustained REM sleep inhibition. Single doses of citalopram resulted in only minor changes in non-REM (NREM) sleep as well as in NREM EEG power spectral density. Chronic administration resulted in a major shift from SWS-2 to SWS-1. The observed corresponding changes in EEG power density were regional. A 30 to 40 percent reduction of power density in the 0.5-15 Hz range in the fronto-parietal EEG derivation was seen for the whole 8-h registration period. In the fronto-frontal EEG derivation only minor changes were seen. A decreasing trend in NREM sleep power density between 0.5 and 7 Hz, usually seen during the course of the light period, was not observed in the chronic condition, but was seen in control and single-dose condition, suggesting altered diurnal distribution of slow wave activity in the chronic condition. The data indicate that acute and chronic administration of citalopram shows clear differences in sleep effect, which may be caused by alteration of serotonergic transmission, and may be related to the antidepressant effect.

[Treatment of chronic insomnia. A recommendation with special emphasis on problems of the elderly]. / Behandling av kronisk insomni. En anbefaling med saerlig vekt på eldres problemer.

Normal physiological changes in sleep occur with increasing age. Most healthy individuals do not perceive these changes in themselves as a health problem. Despite this, chronic insomnia is a common complaint, especially among the elderly. In addition to considerable subjective distress, the symptom of chronic insomnia is associated with increased morbidity and mortality. Thus, a diagnostic evaluation is an essential starting point for rational treatment. The author emphasizes the importance of a multidimensional approach to both diagnosis and treatment. Concentrating on symptom relief only is not enough. Documented treatment modalities are reviewed. There is a discrepancy between the current knowledge and the actual management of sleep disorders. It is concluded that several effective interventions are available. The prevailing nihilism when it comes to treating chronic insomnia is not justified.

Sleep and EEG power spectrum effects of the 5-HT1A antagonist NAN-190 alone and in combination with citalopram.

The sleep and waking and EEG power spectrum effects of the putative 5-HT1A antagonist NAN-190 (0.5 mg/kg, i.p.) were studied alone and in co-administration with the selective serotonin re-uptake inhibitor citalopram (5.0 mg/kg, i.p.) in the rat. Citalopram, as in a prior dose-response study, reduced REM sleep. In addition, a slight increase in NREM sleep was observed. Citalopram reduced NREM fronto-parietal (FP) EEG power density in the 5-20 Hz range. When administered alone, NAN-190 suppressed REM sleep in the first 2 h, and reduced SWS-2 in the first 4 after administration. NAN-190 also suppressed selectively NREM sleep slow-wave activity in both fronto-frontal (FF) and FP EEG power spectrum. When administered in combination with citalopram, an attenuation of the power density reduction in the 7-15 Hz range in the FF EEG of citalopram alone, was observed. However, the EEG power spectral density and REM sleep suppressive effects of NAN-190 were both augmented. The results are compatible with the notion that serotonin is involved in the modulation of the slow wave activity in the EEG during NREM sleep. The results are cordant with other data suggesting that postsynaptic 5-HT1A stimulation might increase slow wave activity in the NREM EEG, and that serotonergic stimulation of other receptor subtypes (possibly 5-HT2) may decrease slow wave activity in the NREM EEG.

Sleep effects following intrathecal administration of the 5-HT1A agonist 8-OH-DPAT and the NMDA antagonist AP-5 in rats.

The modulating effect of an intrathecally (i.t.) administered 5-HT1A agonist and an NMDA antagonist on sleep, waking and EEG power spectra was investigated in rats. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (38 nmol) increased total slow wave sleep (TSWS) and decreased waking over the 8 h recording period. The TSWS increase was mostly due to an increase in SWS1. Sleep latency to SWS1 was also reduced. The NMDA antagonist dl-2-amino 5-phosphonovaleric acid (AP-5) (31.5 nmol) reduced waking. SWS1 was increased, but TSWS was not changed. An increase in REM sleep was seen during the last part of the recording. Combined treatment with 8-OH-DPAT and AP-5 reduced waking and increased TSWS. No change in REM sleep was seen. There were no systematic changes in either waking, TSWS or REM fronto-frontal or fronto-parietal EEG power spectrum after any of the treatments. The results suggest that in the spinal cord stimulation of 5-HT1A receptors have a dampening effect on transmission of sensory information, leading to deactivation and thereby increased possibilities for sleep induction. Blockade of the NMDA receptors may also lead to a small dampening of sensory transmission with similar consequences.

Sleep/waking and EEG power spectrum effects of a nonselective serotonin (5-HT) antagonist and a selective 5-HT reuptake inhibitor given alone and in combination.

Sleep/waking stages, electroencephalogram (EEG) power spectra and behavior were studied in rats for 8 hours following intraperitoneal administration of a nonselective serotonin (5-HT) antagonist (0.1 and 2.0 mg/kg methiothepin) and a selective 5-HT reuptake inhibitor (20 mg/kg zimeldine), given alone and in combination. Consistent with earlier studies, zimeldine gave a biphasic effect on sleep and waking. Waking was increased and slow wave sleep (SWS)-2 decreased initially, followed by an increase in SWS-2 in the second 2-hour period. Rapid eye movement (REM) sleep was reduced throughout the experiment. EEG power densities were generally reduced in the higher frequencies, but the effect differed somewhat in the different vigilance states and between the fronto-frontal and fronto-parietal EEG leads. Zimeldine did not change behavior. Methiothepin, at 0.1 mg/kg, gave only minor effects by itself, but it blocked the initial waking increase of zimeldine. So did 2.0 mg/kg methiothepin, but this dose markedly changed sleep/waking stages by itself: SWS-1 was profoundly increased, whereas waking, SWS-2 and REM sleep were reduced. Total SWS (TSWS) was markedly increased due to the SWS-1 increase. Because TSWS was increased while SWS-2 was decreased following 2.0 mg/kg methiothepin, it is concluded that spindle activity was facilitated, whereas slow wave activity was antagonized. Methiothepin, at 2.0 mg/kg, also markedly changed EEG power densities within TSWS and induced cataleptic behavior. It is concluded that the initial waking increase of zimeldine depends on simultaneous activation of several different 5-HT receptor subtypes. The other zimeldine effects were not consistently antagonized, thus the mechanisms behind these effects remain unclear.

Lesion of descending 5-HT pathways increases zimeldine-induced waking in rats.

Sleep, waking, and EEG power spectra were investigated in rats with spinal 5,6-dihydroxytryptamine (5,6-DHT) lesions, following 20 mg/kg zimeldine or vehicle IP injections. 5,6-DHT selectively lesioned the descending serotonergic pathways. Lesion alone did not change sleep and waking stages compared to baseline, except for a reduction in REM sleep. Consistent with earlier findings, zimeldine in nonlesioned rats increased waking the first 2 h of recording. Zimeldine treatment in lesioned rats gave a significant additional 50% increase in waking the first 2 h and a corresponding decrease in total slow wave sleep, suggesting a potentiation of these effects. Zimeldine gave no significant changes in waking EEG power spectral density. Lesion gave a tendency to reduction between 4.0 and 15.5 Hz compared with baseline, and between 10.0 and 16.5 compared to the independent control group. In both comparisons, the combined treatment strengthened this effect, again suggesting a potentiating effect of lesion. In sleep, zimeldine reduced power over the whole spectrum (0.5-20.0 Hz), less in the lower frequencies than in the higher frequencies.

Diurnal differences in L-tryptophan sleep and temperature effects in the rat.

Sleep/waking and EEG power spectra were investigated for 6 h periods in rats following administration of the essential amino acid L-tryptophan (40 mg/kg), the selective serotonin uptake inhibitor zimeldine (20 mg/kg), and following a combination of L-tryptophan and zimeldine. In contrast to earlier studies, L-tryptophan decreased waking and increased total slow wave sleep when administered late in the light phase (8 1/2 h after light onset). No sleep effects were seen after early light phase injections (2 h after lights on). In agreement with earlier studies, zimeldine initially increased wakefulness, followed by an increase in slow wave sleep-2. REM sleep was abolished after zimeldine treatment. Zimeldine increased EEG delta activity and decreased EEG activity above 7 Hz. L-Tryptophan potentiated the zimeldine induced increase in waking only when given early in the light phase. In a separate experiment, body temperature was monitored after L-tryptophan injections in both early and late light phase. A thermogenic effect of L-tryptophan was seen in the early light phase, while the opposite was seen in the late light phase. The data indicate diurnal differences in sleep/waking and temperature effects of a physiological dose of L-tryptophan.

The reliability and functional validity of visual and semiautomatic sleep/wake scoring in the Møll-Wistar rat.

The present paper has three major objectives: first, to document the reliability of a published criteria set for sleep/wake scoring in the rat; second, to develop a computer algorithm implementation of the criteria set; and third, to document the reliability and functional validity of the computer algorithm for sleep/wake scoring. The reliability of the visual criteria was assessed by letting two raters separately score 8 hours of polygraph records from the light period from five rats (14,040 10-second scoring epochs). Scored stages were waking, slow-wave sleep-1, slow-wave sleep-2, transition type sleep and rapid eye movement (REM) sleep. The visual criteria had good interrater reliability [Cohen's kappa (kappa) = 0.68], with 92.6% agreement on the waking/nonrapid eye movement (NREM) sleep/REM sleep distinction (kappa = 0.89). This indicated that the criteria allow separate raters to independently classify sleep/wake stages with very good agreement. An independent group of 10 rats was used for development of an algorithm for semiautomatic computer scoring. A close implementation of the visual criteria was chosen. The algorithm was based on power spectral densities from two electroencephalogram (EEG) leads and on electromyogram (EMG) activity. Five 2-second fast Fourier transform (FFT) epochs from each EEG/EMG lead per 10-second sleep/wake scoring epoch were used to take the spatial and temporal context into account. The same group of five rats used in visual scoring was used to appraise reliability of computerized scoring. The computer score was compared with the visual score for each rater. There was a lower agreement (kappa = 0.57 and 0.62 for the two raters) than in interrater visual scoring [percent agreement 87.7 and 89.1% (kappa = 0.82 and 0.84) in the waking/NREM sleep/REM sleep distinction]. Subsequently, the computer scores of the raters were compared. The interrater reliability was better than the interrater reliability for visual scoring (kappa = 0.75), with 92.4% agreement for the waking/NREM sleep/REM sleep distinction (kappa = 0.89). The computer scoring algorithm was applied to data from a third independent group of rats (n = 6) from an acoustical stimulus arousal threshold experiment, to assess the functional validity of the scoring directly with respect to arousal threshold. The computer algorithm scoring performed as well as the original visual sleep/wake stage scoring. This indicated that the lower intrarater reliability did not have a significant negative influence on the functional validity of the sleep/wake score.

Sleep stages and EEG power spectrum in relation to acoustical stimulus arousal threshold in the rat.

This study was designed to functionally validate earlier described criteria for visual sleep scoring with respect to acoustical stimulus threshold for arousal. A further objective was to explore the relation between electroencephalographic (EEG) power spectrum and acoustical stimulus threshold for arousal. After habituation to an acoustical stimulus (a 1,000-Hz sine tone, increasing 1.5 dB per second for 45 seconds), values for latency to arousal after acoustical stimulus onset were analyzed. Arousal was determined based on EEG and electromyographic (EMG) criteria. There was a significant effect of sleep stage, with slow wave sleep 2 (SWS-2) having higher arousal threshold than slow wave sleep 1 (SWS-1), rapid eye movement (REM) sleep and transition type sleep. This indicates that the subdivision of nonrapid eye movement (NREM) sleep in the rat into SWS-1 and SWS-2 had functional validity in this paradigm. Time of day also had a significant effect, with lower arousal threshold in the last 2 hours (ninth and tenth hour of the light period) of the 8-hour registration period. Furthermore, there was a significant effect of EEG delta power density. Epochs with high delta power had increased arousal threshold relative to epochs with low arousal threshold. The results were consistent with the notion that delta activity is an indicator of depth within NREM sleep.

Studies on sleep/wake effects of serotonin reuptake inhibitors and receptor subtype involvement.

Studies with the serotonin uptake inhibitors zimeldine and alaproclate show biphasic effects on the sleep/wake axis in rats and cats. Zimeldine induced an initial waking response succeeded by a small SWS-2 increase in rats. The waking increase was not blocked by the 5-HT2 antagonist ritanserin nor by the putative 5-HT1A antagonist (-)-alprenolol. In cats, zimeldine induced initial behavioural changes which were succeeded by a large SWS-2 increase. Alaproclate gave similar initial responses as zimeldine in both species, and was succeeded by a moderate sleep increase in cats but not in rats. The complex sleep/wake effects following the serotonin uptake inhibitors may result from simultaneous induction of incompatible serotonergic effects.

[Inadequate treatment of affective disorders]. / Inadekvat behandling av affektive lidelser.

Inadequate treatment of mood (affective) disorders is related to the mind/body dualism, desinformation about methods of treatment, the stigma of psychiatry, low funding of psychiatric research, low educational priority, and slow acquisition of new knowledge of psychiatry. The "respectable minority rule" has often been accepted without regard to the international expertise, and the consequences of undertreatment have not been weighed against the benefits of optimal treatment. The risk of chronicity increases with delayed treatment, and inadequately treated affective disorders are a leading cause of suicide. During the past 20 years the increase in suicide mortality in Norway has been the second largest in the world. Severe mood disorders are often misclassified as schizophrenia or other non-affective psychoses. Atypical mood disorders, notably rapid cycling and bipolar mixed states, are often diagnosed as personality, adjustment, conduct, attention deficit, or anxiety disorders, and even mental retardation. Neuroleptic drugs may suppress the most disturbing features of mood disorders, a fact often misinterpreted as supporting the diagnosis of a schizophrenia-like disorder. Treatment with neuroleptics is not sufficient, however, and serious side effects may often occur. The consequences are too often social break-down and post-depression syndrome.

[Affective disorders. Drug treatment and electroconvulsive therapy]. / Affektive lidelser. Medikamentell behandling og elektrokonvulsiv terapi.

Optimal treatment of mood disorders and prevention of suicide requires biological and psychosocial methods, therapeutic alliance and psycho-education. In moderate unipolar depression an antidepressant may be sufficient, if necessary potentiated by another antidepressant or triiodothyronine. In moderate bipolar depression lithium or carbamazepine are preferred. In severe unipolar and bipolar depression the combination of an antidepressant and lithium (or carbamazepine) or electroconvulsive therapy (ECT) is indicated, in psychotic depression neuroleptics, too. Non-selective monoamine oxidase inhibitors (MAOIs) are the most potent antidepressants. Moderate acute mania and mixed state may respond to lithium, carbamazepine or valproate only. In severe cases a neuroleptic and lithium are combined, or these drugs may be combined with carbamazepine or valproate. Electroconvulsive therapy is preferable in acute mixed states with marked confusion or depression. In chronic mixed state and rapid cycling, withdrawal of antidepressants and neuroleptics should be tried. Most patients will need a combination of lithium and carbamazepine or valproate. Added to these drugs, antidepressants are less risky. Adding thyroxin may stabilize rapid cycling. The combination of lithium and an antidepressant is the most potent prophylaxis in unipolar disorder and bipolar disorder dominated by depression.

The 5-HT1A antagonist (-)-alprenolol fails to modify sleep or zimeldine-induced sleep-waking effects in rats.

Sleep and waking in rats were studied for 8 h following administration of a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a putative 5-HT1A antagonist (L(-)-alprenolol hydrogene tartrate monohydrate [(-)-alprenolol]) and a combination of (-)-alprenolol and zimeldine. Consistent with earlier findings, zimeldine gave a biphasic effect on sleep and waking. Waking was increased during the first 3 h, followed by a small decrease. Deep slow-wave sleep (SWS-2) showed the opposite trend. An initial decrease in SWS-2 was followed by an increase after around 3 h. Rapid eye movement sleep was markedly suppressed and latencies to sleep increased after zimeldine. (-)-Alprenolol had no effects on the different sleep and waking stages or latencies to sleep. The 5-HT1A antagonist also failed to modify the effects of zimeldine administration. The behavioral syndrome induced by a selective 5-HT1A agonist [8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT)] was clearly antagonized by administration of (-)-alprenolol, indicating that (-)-alprenolol was an efficient 5-HT1A blocker. The data indicate that the sleep-waking effects of zimeldine cannot easily be explained by stimulation of 5-HT1A receptors.