Olanzapine and breast-feeding: changes of plasma concentrations of olanzapine in a breast-fed infant over a period of 5 months.

We here report on a psychotic mother and her breast-fed infant who was treated with olanzapine. Consecutively olanzapine concentrations in the milk and plasma of the mother and in the infant were measured with tandem mass spectroscopy over a period of five month. The results show a relatively high plasma level in the infant aged four month, probably referring to an immature hepatic transformation system, especially CYP1A2. In the following four months plasma levels of olanzapine decreased to very low, even undetectable concentrations in the infant. The infant developed normally and showed no side effects during the treatment period.

A review on hyponatremia associated with SSRIs, reboxetine and venlafaxine.

Hyponatremia, defined as serum sodium below 135 mmol/l, is a potentially life-threatening condition and was shown to be more frequent in elderly and psychiatric patients. In the last years numerous case reports on SSRI- and venlafaxine-induced hyponatremia were published indicating a higher incidence than previously thought. Only few studies have been performed and the incidence reported varies widely from 4.6/1000 people to 25%. It is still unclear if any single SSRI shows a higher incidence of hyponatremia than the others. Some data suggest that venlafaxine may have a stronger association to hyponatremia than SSRIs. Risk factors include age, female sex, low body mass index, severe physical illness, history of former hyponatremia and co-medications known to induce hyponatremia, especially thiazide diuretics. Symptoms of hyponatremia are usually neuropsychiatric (e.g. restlessness, lethargy, cognitive impairment), and any worsening in psychiatric symptoms in patients with a corresponding risk-profile receiving SSRIs or venlafaxine should give cause to check serum electrolytes. Usually SSRI-induced hyponatremia occurs within approximately 30 days and is reported to improve after withdrawal of the drug. Further controlled studies to confirm the true incidence of hyponatremia due to SSRI or venlafaxine and to define predictors more precisely are needed.

Intravenous versus oral administration of amitriptyline in patients with major depression.

Antidepressants can be administered by different routes. Advantages for either the oral or the intravenous administration have been suggested from pharmacokinetic as well as from clinical points of view. Controlled comparison studies of the two routes do not provide unequivocal recommendations. In this investigation, amitriptyline was studied over a 4-week period consisting of a 2-week, double-blind/double-dummy phase with either oral (150 mg/day), high-dose intravenous (150 mg/day), or medium-dose intravenous (100 mg/day) treatment and a 2-week phase of open oral treatment in 80 patients with major depression. A psychopathologic assessment was made using the Hamilton Rating Scale for Depression, the Clinical Global Impressions Scale, the von Zerssen's "Befindlichkeitsskala," an adjective checklist, and a Visual Analog Scale. No significant differences were found concerning the mean scores of the rating scales or time of onset of action in the physicians' ratings. In the patients' self-ratings, there was an earlier therapeutic effect in the high-dose intravenous group. The number of improvers after 7 days was significantly higher in the high-dose intravenous group compared with both other groups. After 14 days, no significant differences in the numbers of improvers and responders between groups were detected. The results of this study do not clearly favor one of the tested options. The main differences found in this study seem to be dose-related rather than differentiating between oral and intravenous routes of administration.

Tyrosine hydroxylase immunoreactivity in the locus coeruleus is reduced in depressed non-suicidal patients but normal in depressed suicide patients.

Noradrenergic neurons of the locus coeruleus (LC) have been implicated in the neurobiology of depression and suicidal behavior. The current postmortem study determined numbers of noradrenergic neurons by immunostaining the synthesizing enzyme tyrosine hydroxylase in the LC of 12 non-elderly depressed patients with a mood disorder as compared to 12 age- and sex-matched normal controls. Six patients were suicide victims, the other six patients died of natural causes. Non-suicidal patients had fewer neurons immunoreactive for tyrosine hydroxylase (TH-ir) than suicide victims or controls. No difference appeared between the number of TH-ir neurons in suicide patients and controls. Numbers of pigmented LC neurons were equal in patients and controls. The differences of TH-immunoreactivity could neither be attributed to drug influences nor to polarity of depressive disorder (i.e., unipolar/bipolar). Numbers of TH-ir neurons correlated positively with mean doses of tri- or tetracyclic antidepressants. Results of this study suggest a presynaptic noradrenergic deficit of the LC in depressed non-suicidal patients. Indirect evidence is provided that suicide is not related to decreased noradrenergic function and that traditional antidepressants may enhance noradrenergic activity of the LC in depressed patients.

Infusional high-dose application of the calcium-channel-blocking and antiglutamatergic agent caroverine in the treatment of alcohol withdrawal (DSM-III-R 291.80).

In an open study, nineteen in-patients fulfilling the criteria for an alcohol withdrawal syndrome (DSM-III-R 291.80) were treated with intravenous caroverine (400 mg/12 h). Caroverine is a class B calcium-channel-blocker and antiglutamatergic agent with significant effects on the brain function. Caroverine exhibits competitive AMPA antagonism, and at higher concentrations, non-competitive NMDA antagonism. All rating scales showed a significant improvement from the start of the treatment throughout the whole study period (CIAW-Ar: P=0.0000; NGI 1: P=0.0000, NGI 2: P=0.0304; CGI 1: P=0.0000, CGI 2: P=0.0208, CGI 3: P=0.0003). The heart rate also stabilised from 111/min before treatment to 81/min after 12 h (P=0.0000). Caroverine was well tolerated, showed no sedative side effects, and no epileptic seizures were observed.

Propofol and methohexital as anesthetic agents for electroconvulsive therapy (ECT): a comparison of seizure-quality measures and vital signs.

In a randomized crossover study, the influence of the anesthetics methohexital and propofol on EEG seizure parameters, seizure-quality measures, vital signs, and oxygen saturation (SpO2) and end-tidal carbon dioxide tension (ETCO2) was investigated; 146 treatments of 31 patients were analyzed. Significant differences were observed between agents for mean postictal pulse and blood pressure values. With methohexital, there was a clear postictal increase of mean blood pressure from 126/78 mm Hg to 161/102 mm Hg, whereas there was no increase with propofol (p = 0.00), and with methohexital, a postictal increase of the mean pulse rate from 81 to 90 beats/min and a slight decrease with propofol (79 to 78 beats/min). There were no differences in the SpO2 and ETCO2. The mean seizure duration for unilateral treatments was significantly longer with methohexital (52.7 s) compared with propofol (34.1 s; p = 0.000), but there was no difference for the seizure-quality measures: postictal suppression index (propofol 79.7%, methohexital 77.4%) and mean integrated amplitude (30.2/31.8) were the same for both anesthetic agents. The results show that differences in seizure duration are unrelated to seizure-quality measures.

Risperidone in the treatment of schizophrenia: results of a study of patients from Germany, Austria, and Switzerland.

Results of a subanalysis of data from the multinational risperidone trial (RIS-INT-2) are reported. Patients with chronic schizophrenia were treated with risperidone at 1 mg/day (n = 25), 4 mg/day (n = 27), 8 mg/day (n = 29), 12 mg/day (n = 31), or 16 mg/day (n = 29), or 10 mg/day of haloperidol for 8 weeks. According to the Positive and Negative Syndrome Scale (PANSS) total and subscale scores, improvements were noted in each treatment group from baseline to treatment endpoint. On each scale the magnitude of improvement was greater in the risperidone patients than in the haloperidol patients. The onset of action of risperidone was faster than haloperidol. By treatment week 2, over half of the patients receiving > or = 4 mg/day of risperidone were clinically improved (> or = 20% reduction in total PANSS scores). This rate of improvement was not seen until week 6 in the haloperidol patients. Severity of extrapyramidal symptoms (scores on the Extrapyramidal Symptom Scale) was significantly lower in patients receiving 1 or 4 mg/day of risperidone than in patients receiving higher risperidone doses and in haloperidol patients. The optimal dose of risperidone, in terms of both efficacy and safety, was 4 mg/day. These results confirm the findings of the controlled trials of risperidone conducted in North America and the multinational trial.

Multicenter double blind study of paroxetine and amitriptyline in elderly depressed inpatients.

Paroxetine is a phenylpiperidine compound which is a selective serotonin reuptake inhibitor (SSRI). Ninety-one hospitalised patients with a major depression (DSM-III) aged 65 and over from six Austrian and one German center were entered into the study, which compared the efficacy and tolerability of paroxetine versus amitriptyline. After 6 weeks both groups showed similarly good therapeutic results. In the paroxetine group, 64.3% of the patients had a 50% or more reduction of the HAMD total score compared to 58.1% in the amitriptyline group. Side effects were distributed similarly in both groups. Patients in the paroxetine group showed a higher incidence of anxiety and agitation; anticholinergic side effects were registered more often in the amitriptyline group.

Ipsapirone in the treatment of bulimia nervosa: an open pilot study.

Seventeen women who met the criteria for bulimia nervosa (DSM-III-R) were treated for 4 weeks in an open trial with ipsapirone, a partial 5-HT1A agonist. Bulimic symptoms diminished in 66.6% of the patients after only 1 week of treatment, 93.3% showed a reduction of more than 50% of weekly binge eating attacks after 4 weeks. The mean frequency of binges was reduced by 81% at endpoint. Ipsapirone was well tolerated.

A multicenter double-blind trial of paroxetine versus amitriptyline in depressed inpatients.

The phenylpiperidine derivative paroxetine is a selective serotonin reuptake inhibitor. In a double-blind 6-week trial, paroxetine was compared with amitriptyline in hospitalized patients suffering from major depression (DSM-III). One hundred fifty-three patients were enrolled in the study in seven centers in Austria and Germany. Results showed similar efficacy of both drugs after 6 weeks. The differences between groups in Montgomery-Asberg Depression Rating Scale and Clinical Global Impression ratings did not reach statistical significance at any time. Side effects were distributed similarly but with a significantly higher incidence of anticholinergic effects in patients treated with amitriptyline (p < or = 0.001), whereas agitation and insomnia were registered more often in the paroxetine group. This study supports the antidepressive efficacy of paroxetine in a sample of severely depressed inpatients.

Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects.

The efficacy of paroxetine and fluoxetine and their effects on cognitive and behavioural function were compared in a 6 week, double-blind, randomized study of 106 elderly depressed patients (aged 61 to 85 years). Antidepressant efficacy was assessed using the Hamilton depression rating scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) scale. The Sandoz Clinical Assessment Geriatric scale (SCAG), the Mini-Mental State Examination (MMSE), and HAMD cognitive factor scores were used to assess cognitive and behavioural function. Paroxetine demonstrated comparable efficacy to fluoxetine in the treatment of elderly depressed patients, but at the end of treatment, there was a significantly higher proportion of responders to paroxetine than to fluoxetine. Both treatments produced improvements in all measures of cognitive and behavioural function, but paroxetine was significantly superior to fluoxetine from Week 3, indicating a possible early effect. There was no difference between the two agents in either the tolerability or safety of treatment.

A double-blind comparative multicentre study of controlled-release remoxipride, immediate-release remoxipride and haloperidol in schizophrenia.

A double-blind multicentre study comparing the efficacy and safety of remoxipride in controlled-release formulation (REM-CR), given once a day, and immediate-release formulation (REM-IR) and haloperidol, given twice daily, was conducted in patients with schizophrenic illness. In total, 150 inpatients were randomized: 49, 51 and 50 in the REM-CR, REM-IR, and haloperidol groups, respectively. The mean daily dose of REM-CR during the last week of treatment was 361 mg, that of REM-IR 332 mg. In the haloperidol group the corresponding dose was 12.5mg per day. The study treatment period was four weeks. The median BPRS total score was 37.5 in the REM-CR group at start of treatment, and 14.5 at last rating (n = 38). For the REM-IR group and the haloperidol group the corresponding figures were 36.0 and 38.0 at start of treatment and 18.0 (n = 43) and 16.5 (n = 40) at last rating. No statistically significant differences were found between the treatments. Therapy-emergent extrapyramidal symptoms (Simpson & Angus rating scale) were significantly (p less than 0.05) more frequent and more severe during haloperidol than during REM-CR and REM-IR treatment, despite significantly higher concurrent use of anticholinergic drugs in the haloperidol group.--REM-CR was comparable in efficacy and tolerability to REM-IR. The tolerability profile favoured both remoxipride formulations over haloperidol. Evaluation of the clinical chemistry, haematology, and cardiovascular data showed no clinically significant deleterious effects on any organ system for either drug.

Efficacy and safety of moclobemide compared with imipramine in the treatment of major depressive disorder. Double-blind multicenter study, Austria.

In a double-blind, 4-week, prospective, randomized multicenter (17 centers) study we checked on the efficacy, tolerability and safety of moclobemide (300-600 mg/d) compared to imipramine (100-200 mg/d) in parallel groups of patients with a Major Depressive Episode (DSM III). The mean % reduction of the HAMD at the end of treatment was 51.7 in the moclobemide group and 52.1 in the imipramine group. The percentage of patients in whom efficacy was globally judged as "good" or "very good" was 62% in the moclobemide group and 60% in the imipramine group. There was no statistically significant difference in the efficacy in both groups but in some factors there was a trend for a better amelioration favoring moclobemide. The final overall physician's judgement of tolerability was "good" or "very good" in 83% of moclobemide patients and in 74% of imipramine patients. Adverse events were reported or observed in 56% of moclobemide patients and in 69% of imipramine patients. The number of mild, moderate and severe adverse events was higher in the imipramine group with a total of 286 versus 189. There was a statistically high significant difference considering the tolerability favoring moclobemide again. In this project the basic goal to find a substance with at least the same efficacy but a much better tolerability for sure got fulfilled.

Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM-III): an Austrian double-blind, multicentre study.

The antidepressant efficacy, tolerability, and safety of moclobemide, a reversible, monoamine oxidase-A inhibitor, were compared with those of imipramine in parallel groups of patients with a major depressive episode, in a 4-week, multicentre (17 centres), randomised study. A total of 381 patients were randomly allocated to either treatment; they were not required to avoid tyramine-rich foods. Drop-out rates were comparable in both groups at about 17%. Judged primarily on the HRSD, no significant differences in efficacy were observed between the groups, but the number of patients presenting with adverse events, as well as the total number of adverse events, was greater with imipramine. Cardiovascular tolerability was satisfactory and physical examination, body weight, and laboratory values were essentially unaffected in both groups.

[Computed tomography and the clinical picture of suicidal CO poisoning]. / Computertomographie und Klinik bei suizidalen CO-Vergiftungen.

Cranial CT is important to exclude the presence of a mass in the cavum cranii in case of an unclear suicide attempt, particularly a traumatic mass. It can be helpful also in cases of carbon monoxide intoxications.

[Electroconvulsive therapy (ECT)]. / Elektrokonvulsivtherapie (ECT).

The present review of about 250 relevant publications should give a survey of the current state of electroconvulsive therapy (ECT), which is one of the oldest somatic treatments in psychiatry. It deals with the history of convulsive therapy, comparing studies, biological foundations of ECT, indications, contra-indications and risks, effects on various organs, drug interactions, effects of the electrode-placement and stimulus-waveforms, as well as the application of ECT. The final part can be seen as a reference for practical application of (unilateral non-dominant) ECT.