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.

Olanzapine plasma concentration in a newborn.

Little is known about the use of antipsychotics in pregnancy and the corresponding plasma levels in the newborn child. We report on a woman with schizophrenia treated with olanzapine during pregnancy. Plasma levels of olanzapine were assessed both from the mother and from umbilical cord. The plasma level of the newborn (11 ng/mL) was about one third compared to the mother (range 25-34 ng/mL).The development of the fetus, delivery and the development of the child during the first six months were normal.

Intravenous mirtazapine is safe and effective in the treatment of depressed inpatients.

Mirtazapine is a third-generation antidepressant with a dual mode of action. The oral administration has been shown to be effective and safe in the treatment of depressed patients. In this multicenter naturalistic study, we assessed the safety, tolerability, and therapeutic efficacy of intravenously administered mirtazapine in 80 moderately to severely depressed inpatients during a treatment period of 14 days. We found a significant decrease of the Hamilton Depression Rating Scale total score compared to baseline. Side effects were mild and transient. Our data indicate that intravenous mirtazapine is an effective, safe and well-tolerated treatment for depressed inpatients.

Cardiomyopathy after long-term treatment with lithium - more than a coincidence?

We describe a patient suffering from dilative cardiomyopathy after 16 years of treatment with lithium carbonate. The literature concerning lithium and cardiac adverse reactions is briefly reviewed. There is good evidence for acute cardiac reactions, especially cardiac arrhythmia but a rather speculative association with long-term reactions such as cardiomyopathy. Nevertheless clinicians should be aware of this rare but life threatening conjunction of cardiac disease and lithium treatment.

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.

Risperidone and breast-feeding.

We present the case of a breast-feeding woman with acute psychotic symptoms after delivery, which were treated with the antipsychotic agent risperidone. Serum levels of risperidone and 9-hydroxyrisperidone could be detected in both the mother and her infant. Drug-levels in breast milk were ten-fold lower compared to maternal serum. The patient responded well to antipsychotic treatment. Her infant did not display any adverse effects and psychomotor development was normal. In this case, risperidone was a safe treatment option for the breast-feeding mother and her infant. We also provide a brief overview of the clinically relevant data concerning antipsychotics and breast-feeding.

Hippocampal volume reduction in male schizophrenic patients.

Using magnetic resonance imaging of the brain, we examined volumetric measurements of total brain, hemispheres, lateral ventricles and the hippocampus/amygdala complex in male subjects (41 first-episode schizophrenics, 30 chronic schizophrenic patients and 32 healthy controls). We found significantly smaller total brain size in the chronic schizophrenic group, significantly larger lateral ventricles in both patient groups and hippocampal volume reduction bilaterally in first-episode patients (-13.2% left, -12.05% right) and chronic patients (-10.6% left, -10.5% right) compared to controls--irrespective of diagnostic subtype, family history for psychiatric diseases, psychopathology, duration of illness or age at onset.

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.

Assessment of the alcohol withdrawal syndrome--validity and reliability of the translated and modified Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-A).

The alcohol withdrawal syndrome is a common phenomenon in psychiatric hospital care. Not only treatment strategies, but also the evaluation of the syndrome, are discussed controversially. The most widely used instrument is the Clinical Institute Withdrawal Assessment-Alcohol (CIWA-A) and the succeeding CIWA-Ar. We modified the CIWA-A and translated it into German. Validity and reliability of the modified and translated scale were analysed by several psychological tests as well as different somatic measures in 31 patients. The German version appears to be a valid and reliable instrument for the assessment of alcohol withdrawal syndrome useful for clinical routine as well as treatment trials.

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.

Carbamazepine in the prophylaxis of major depression: a 5-year follow-up.

BACKGROUND: The prophylaxis of unipolar depression is still controversial. Some physicians prefer lithium, others maintenance treatment with antidepressants. The role of carbamazepine remains unclear. Only a few patients have been described in the literature; most are lithium nonresponders or rapid cyclers. METHODS: In an open-label naturalistic study, 15 patients suffering from major depression with melancholia (DSM-III, 296.2, 296.3) and receiving long-term prophylaxis with carbamazepine were followed for 5 years. Four had been pretreated with lithium without satisfactory effects, 11 were prophylaxis naive. We compared the number of depressive episodes before and during carbamazepine treatment. RESULTS: The mean time span patients received carbamazepine was 49.5 months. Seventy-three percent (11 of 15) of the patients gained substantial benefit from carbamazepine. Side effects were infrequent. CONCLUSION: Our results encourage further controlled and prospective studies using carbamazepine for maintenance treatment of patients with unipolar major mood disorder.

The role of carbamazepine in the prophylaxis of unipolar depression.

The prophylaxis of unipolar depression is still a controversial subject. Some authors prefer lithium, others maintenance treatment with antidepressants. The role of carbamazepine remains unclear. Few patients have been described in the literature, and most are lithium nonresponders or rapid cyclers. In an open-label naturalistic study, 15 patients suffering from unipolar depression (DSM-III, 296.2, 296.3) and receiving long-term prophylaxis with carbamazepine were followed for 5 years. Four had been pretreated with lithium without satisfactory effects, 11 were prophylaxis naive. The mean time span patients received carbamazepine was 49.5 months. 73% of the patients gained substantial profit from carbamazepine. Side effects were infrequent.

Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study.

The use of more than 130 drugs and drug combinations against the alcohol withdrawal syndrome reflects the fact that views on its treatment are far from being unequivocal. Benzodiazepines are the first choice treatment but it should not be disregarded that they have side effects and, above all, a varying risk of dependency themselves. In recent years many trials have focused on carbamazepine in this respect. Its efficacy was proven in various open and double-blind studies, most of them using concomitant sedative drugs, thereby diminishing the reliability of the results. In a double-blind study we compared the efficacy of carbamazepine with that of oxazepam, in 60 in-patients suffering from alcohol withdrawal syndrome. The main rating instrument was the Clinical Institute Withdrawal Scale--Alcohol (CIWA-A). The 7-day trial showed equal efficacy of carbamazepine and oxazepam during the first 5 days and a statistically significant superiority of carbamazepine on days 6 and 7. Four patients in each group had to be dropped from the study due to side effects or after having withdrawn informed consent. There was no decrease in white blood counts under carbamazepine. The experiences with carbamazepine up to now suggest a more widespread use, especially in non-delirious withdrawal states.

Carbamazepine monotherapy in the treatment of alcohol withdrawal.

More than 135 different strategies for medical treatment have been described for the treatment of alcohol withdrawal syndromes. The substances used most frequently (benzodiazepines, barbiturates, or clomethiazol) themselves pose some risk for abuse or addiction. Anticonvulsants, especially carbamazepine (CBZ), have been discussed for the treatment of alcohol withdrawal since the early seventies. Various studies report favourable results with CBZ, usually combined with sedative agents. Nineteen out-patients and 19 in-patients took part in an open study of CBZ in alcohol withdrawal. The dose of CBZ was adjusted individually and ranged from a mean dose of 761 mg on day 1 to 616 mg on day 3 and to 388 mg on day 7 in the group of out-patients, and from 789 mg on day 1, 694 mg on day 3 to 562 mg on day 7 in the sample of in-patients. The "Objective Clinical Scale in Assessment and Measurement of Alcohol Withdrawal" (OCSAMAW) was used for treatment evaluation. Statistical analysis showed a significant improvement on the 5%-level in both groups; four in-patients needed concomitant treatment with oxazepam. Nausea and pruritus were the most common side-effects of CBZ treatment.

Carbamazepine in the prophylaxis of mood disorders.

Alternatives to lithium are desirable in the prophylaxis of affective disorders, especially in patients who are intolerant of or do not respond to that drug. In the past few years the anticonvulsant carbamazepine has been in the foreground of discussion. Twenty-four patients with affective disorders (17 unipolar depressed, six bipolar, and one unipolar manic) were included in a comparative trial of lithium and carbamazepine; 12 had been pretreated with lithium without a satisfactory effect. All patients received carbamazepine (four received it in combination with lithium) over a mean time span of 20.2 months. Eighty percent of the patients improved with carbamazepine treatment. Side effects were infrequent.