Henner Giedke

Lithium versus carbamazepine in the maintenance treatment of bipolar disorders - a randomised study

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; lithium serum level: 0.63 +/- 0.12 mmol/l, carbamazepine dose: 621 +/- 186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (P = 0.041) and/or adverse effects (P = 0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years; P = 0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P = 0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.

Daytime variations in central nervous system activation measured by a pupillographic sleepiness test.

Pupil size is regulated exclusively by the autonomic nervous system, and in darkness is proportional to the level of central sympathetic tone. Spontaneous pupillary movements, while at rest in darkness and quiet, were recorded for a period of 11 min, using infrared video pupillography. Thirteen young adults took part in a 30‐h experiment lasting from 08.00 h to 14.00 h on the following day. Pupillographic testing and completion of a self‐rated scale for the estimate of sleepiness were repeated every two hours. Pupillary unrest index (PUI), as a measure of pupil size instability associated with daytime sleepiness, showed the lowest values at 09.00 h, when pupil size was found to be maximal, and 23.00 h. During the course of the day, amplitude spectrum ≤0.8 Hz and PUI showed increasing values during the afternoon hours, followed by a decrease during the evening. Daytime variations in the pupillary unrest index in healthy normal subjects were found to be positively correlated with the level of alertness. These findings are similar to the daytime variations found by the MSLT (multiple sleep latency test) in young adults.

Lithium vs carbamazepine in the maintenance treatment of schizoaffective disorder: a randomised study

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in schizoaffective disorder. A total of 90 ICD-9 schizoaffective patients were included in the maintenance phase (2.5 years). They were also diagnosed according to RDC and DSM-III-R and classified into subgroups. Mean serum levels were 0.58±0.12 mmol/l for lithium and 6.4±1.5 μg/ml for carbamazepine (mean dose 643±179 mg/d). Outcome criteria were hospitalisation, recurrence, concomitant psychotropic medication and adverse effects leading to discontinuation. There were more non-completers under carbamazepine than under lithium (p=0.02). Survival analyses demonstrated no significant differences between lithium and carbamazepine in treatment outcome. Patient’s ratings of side effects (p=0.003) and treatment satisfaction (p=0.02) favoured carbamazepine. Following the RDC criteria, patients of the schizodepressive and non-classifiable type did better under carbamazepine (p=0.055 for recurrence), whereas in the schizomanic patients equipotency of both drugs was found. Applying DSM-III-R, carbamazepine demonstrated a superiority in the patient group with more schizophrenia-like or depressive disorders (p=0.040 for recurrence), but not in patients fulfilling the DSM-III-R criteria of bipolar disorder. Lithium and carbamazepine seem to be equipotent alternatives in the maintenance treatment of broadly defined schizoaffective disorders. However, in subgroups with depressive or schizophrenia-like features and regarding its long-term tolerability carbamazepine seems to be superior.

Direct comparison of total sleep deprivation and late partial sleep deprivation in the treatment of major depression

BACKGROUND There are clinical as well as experimental indications that--contrary to what is generally assumed--late partial sleep deprivation (LPSD) is not as effective as total sleep deprivation (TSD) in the treatment of depression. METHOD We conducted a randomised balanced crossover study with 39 in-patients with major depression (mainly unipolar) in which both procedures LPSD and TSD were compared within a 1-week interval. Response was defined as a reduction of > or =30% in the 6-item Hamilton Depression Rating Scale and/or one of two self-rating scales (Adjective Mood Scale, Visual Analogue Scale). RESULTS Overall response rate on the day after was low (0-53%, depending on the rating used). TSD proved slightly and in about half of the comparisons also significantly more effective than LPSD. In general, first treatments were more effective than second treatments; there were 10-20% second day responses; in up to 10% of the treatments patients worsened after sleep deprivation (using the same absolute criteria as for therapeutic response). LIMITATIONS Non-blind rating, intentional and unintentional napping (microsleep) was not recorded, mainly unipolar depressives. CONCLUSIONS Total sleep deprivation seems to be more effective than late partial sleep deprivation. We believe that there might be a dose-response relationship between hours of lost sleep and therapeutic effect within the range of 1 night.

The timing of partial sleep deprivation in depression

In 26 major depressed and 4 schizoaffective inpatients (according to the RDC) early and late partial sleep deprivation (PSD) were carried out. For most of the patients (N = 25) this was done in a balanced crossover design. Residual sleep, starting at 21:00 or 2:00 respectively, was recorded polygraphically. Total sleep time was held constant between the 2 conditions (168 +/- 46 min in early sleep, 173 +/- 28 min in late sleep). Mood ratings with 5 different measures on the 2 days following each PSD revealed significant therapeutic effects from both procedures with only minor differences between them. Thus, sleep reduction as such and not the time at which it takes place (first or second half of the night) appears to be the therapeutic agent in PSD.

The recruitment process for a multicenter study on the long-term prophylactic treatment of affective disorders '

The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders. Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons. Further, a number of patients equal to that eventually allocated to the trial refused to participate for personal, idiosyncratic reasons. In spite of this, the patients in the trial were very similar to those not participating with respect to relevant variables such as age, sex, number of and intervals between previous episodes or severity of the present episode.

Plasma levels, psychophysiological variables, and clinical response to amitriptyline

Hamilton depression scale ratings and physiological measurements were made for 37 patients with primary depression before treatment with amitriptyline (150 mg/day) and again after 2 and 4 weeks of treatment; plasma drug levels were determined weekly. Improvement was maximal at mean amitriptyline + nortriptyline concentrations of 125-200 ng/ml (14 patients), while at lower levels the outcome was significantly poorer (12 patients). Highly variable results were seen in 11 patients with levels between 200 and 301 ng/ml, with lesser improvement occurring in those patients who exhibited poor habituation of the skin resistance response before treatment. Other psychophysiological variables showed significant changes during treatment, but no correlation with clinical results or drug levels.

Validation of a therapeutic plasma level range in amitriptyline treatment of depression.

In the course of a double-blind study, 29 depressed patients received amitriptyline 150 mg/day for 4 weeks. Scores on the Hamilton Depression Rating Scale were assessed before treatment and after 2 and 4 weeks, and plasma levels of amitriptyline, nortriptyline, and (E)-10-hydroxynortriptyline were monitored weekly. Response reflected by percent reduction of Hamilton Depression Rating Scale score and by final score was better at steady-state amitriptyline + nortriptyline concentrations of 125-210 ng/ml than at lower and higher plasma levels. This applied to the total group and to the subgroup of 22 female patients. The data confirm the results of a previous study performed in the same hospital. An influence of the (E)-10-hydroxynortriptyline concentration in plasma on therapeutic outcome was not discernible. The results suggest that plasma level monitoring may be helpful when patients do not respond to conventional amitriptyline doses.

Psychophysiology of anxiety, fear and phobia

Abstract 1. 1. First, the authors present a brief outline of the concepts of anxiety, fear and phobia and their physiological concomitants. 2. 2. Experimental findings are then presented showing that the emotional state of anxiety is generally linked to physiological activation as measured in spontaneous fluctuations and habituation rate of the orienting response of the galvanic skin response (GSR). 3. 3. Other findings show that on the contrary, depression is linked to inhibition or disactivation of these systems, and also of contingent negative variations (CNV). 4. 4. In unselected samples of anxious-depressed patients, the above relationships do not become obvious when psychopathology is self-rated, which suggests that anxiety and depression are better distinguished by the examining physician than by the patients themselves.

Single-dose kinetics of the neuroleptic drug perazine in psychotic patients

Eight male and two female unmedicated psychotic patients received 100 mg perazine orally and seven blood samples were taken within 25 h. Plasma levels of perazine and its demethylated metabolite were analyzed by HPLC with electrochemical detection. They exhibited large interindividual variations, with maximal concentrations as well as AUC values of perazine differing more than 10-fold. From the decay of plasma levels during the last 12–18 h half-lives were estimated to be between 7.5 and 16 h; they did not correlate with AUC. There was a significant positive correlation between AUC and age. Desmethylperazine was consistently present at lower concentrations than the parent drug during the first 12 h.