[Somatic disease at a department for acute psychiatric disease]. / Somatisk sygdom hos patienter i en akut psykiatrisk modtageafdeling.

All of the patients admitted to the psychiatric inpatient department of the Municipal Hospital in Copenhagen during a period of three months were, on discharge, registered as regards somatic disease. 70% (95% confidence limits 66-75%) had somatic disease (38% of these were newly diagnosed). Treatment of these was carried out by the medical staff of the department and in 46% of the cases this was carried out in cooperation with the medical staffs of somatic departments. The close geographic contact with the departments for somatic diseases facilitated this cooperation. The staff in departments for emergency inpatient treatment of psychiatric disease should be able to observe and treat somatic disease on account of the high incidence of this. A psychiatric/medical special department could probably provide optimal treatment in cases of combined psychiatric and somatic disease.

[Organic disease among patients at an open psychiatric outpatient clinic]. / Organisk sygdom hos patienter i en åben psykiatrisk modtagelse.

All of the new consultations in the Copenhagen Municipal psychiatric outpatient department during a period of three month were registered. Out of these, 1,149 did not lead to admission of the patient. In 47% of these information about somatic condition was available and in 31% information about somatic disease was present. Were 21% of the 1,149 patients were concerned, there were indications for treatment of the somatic disease. 50% of these were treated by the medical staff of the department, 17% were treated in other psychiatric departments, 21% were treated in departments for somatic disease and 11% were referred to their general practitioners or practising specialists for further treatment. These findings emphasize the importance of medical referral in an open psychiatric clinic with direct therapeutic contact.

Zimeldine versus nomifensine. A double-blind study of depressed inpatients.

A double-blind comparison of zimeldine, a selective 5-HT reuptake inhibitor, and nomifensine, a noradrenaline and a dopamine reuptake inhibitor, was carried out in 43 inpatients with a scheduled treatment period of 6 weeks. All patients were diagnosed as definite major depressive disorder according to Research Diagnostic Criteria (RDC), and the WHO International Classification of Diseases (ICD-9). The antidepressive efficacy was evaluated by a 10-item subscale of the Comprehensive Psychopathological Rating Scale (CPRS), a clinical global impression (CGI) scale and a self-rating scale (VAMS). Side effects were recorded, and anticholinergic effect was evaluated by parotid saliva volume measurement. No statistically significant differences in efficacy or profile between the two drugs were demonstrable. With the exception of increased sweating in the zimeldine group there were no statistically significant differences in side effects.

Methylphenidate, apomorphine, THIP, and diazepam in monkeys: dopamine-GABA behavior related to psychoses and tardive dyskinesia.

In eight monkeys (Cercopithecus aethiops), previously treated with haloperidol for 4-14 months, we have examined the behavioral effect of: (1) methylphenidate vs apomorphine; (2) 4,5,6,7-tetrahydroisoxazolo-(5,4-c)-pyridin-3-ol(THIP, a GABA agonist) vs diazepam; and (3) THIP and diazepam in methylphenidate-induced behavior. Methylphenidate (0.5-5.0 mg/kg) and apomorphine (0.1-0.5 mg/kg) both increased locomotion, but otherwise exhibited different behavioral profiles. Methylphenidate induced repetitive movements of head, limbs, and trunk, and hallucinatory-like behavior, but not oral hyperkinesia (licking and gnawing), whereas apomorphine preferentially caused oral hyperkinesia. THIP produced a syndrome of bradykinesia, dystonia, ataxia, myoclonus, sedation, and decreased responsiveness, whereas diazepam produced only bradykinesia, ataxia, sedation, and decreased responsiveness, but not dystonia and myoclonus. Methylphenidate-induced locomotion and repetitive movements were reduced by THIP and diazepam, whereas hallucinatory-like behavior was markedly aggravated by THIP, but not by diazepam.

Serum concentrations of cis(Z)-flupentixol and prolactin in chronic schizophrenic patients treated with flupentixol and cis(Z)-flupentixol decanoate.

Nine chronic schizophrenic patients selected from three hospital departments were treated with flupentixol (orally and IV) and cis(Z)-flupentixol decanoate in Viscoleo (IM) in a three-phase pharmacokinetic study. Oral administration (single and repeated dosage) showed a relatively slow absorption with maximum serum concentration around 4 h after administration. Intravenous injection indicated multicompartment kinetics for cis(Z)-flupentixol. The biological half-lives calculated after the different doses were the same, indicating that the pharmacokinetics of cis(Z)-flupentixol does not differ between single and repeated administration and does not change when moderately higher doses are given. The bioavailability of orally administered cis(Z)-flupentixol was calculated to be about 40% with IV injection as reference. After IM administration maximum serum concentration was seen between 4 and 10 days in most patients. Calculation of a disappearance half-life gave very variable results, indicating that the release of the drug from the oil depot is not a monoexponential process. The intramuscular depot had a much lower bioavailability than IV injection, which means that steady state has not been obtained after 8 weeks of depot treatment. Serum prolactin concentrations were elevated during neuroleptic treatment, but no correlation was found between prolactin concentrations and the serum concentrations of cis(Z)-flupentixol. A correlation between the changes in clinical ratings and concentrations of cis(Z)-flupentixol or prolactin was not found.

Levodopa and receptor sensitivity modification in tardive dyskinesia.

Tardive dyskinesia (TD), a syndrome of involuntary hyperkinetic movements, purportedly involves the development of dopamine (DA) receptor hypersensitivity following long-term receptor blockade with neuroleptic drugs. It has been proposed that through a process of receptor hypersensitivity modification, TD can be treated by reversing the receptor hypersensitivity with DA agonists. Thirteen patients with TD were treated for 4--8 weeks with levodopa plus benserazide, a peripheral decarboxylase inhibitor (Madopar, Roche, Basel, Switzerland) over a wide dose range corresponding to 3.0--9.0 g/day levodopa. Drug effects was assessed by blind evaluations of randomly sequenced videotapes made before, during, and for 6 weeks following treatment. TD scores moderately increased during levodopa. After the drug was discontinued, TD scores returned to pretreatment baseline levels without further improvement in those patients receiving concurrent neuroleptic medications (N = 9), but in the neuroleptic-free patient TD scores decreased 25% in three patients and were resolved in one younger patient. Psychological effects of depression or increased psychotic symptoms occurred at higher drug doses. These results do not support the proposal that receptor sensitivity modification with levodopa is an effective therapeutic approach to TD, though selected patient and drug treatment variables, including other DA agonists, are considerations for further investigation.

Enkephalin, morphine, and naloxone in tardive dyskinesia.

Eight psychiatric patients with tardive dyskinesia (TD) were treated with single doses of the synthetic met-enkephalin analogue FK 33-824 (1, 2, and 3 mg IM) morphine (10 mg SC) and naloxone, an opiate receptor antagonist (0.8 mg IM). The drug effects were assessed by blind evaluation of randomly sequenced videotapes made before and during treatment. FK 33-824 (1, 2, and 3 mg IM) slightly reduced TD (P < 0.05) and increased preexisting bradykinesia. The effect on TD, however, was pronounced only in patients concurrently treated with neuroleptics in relatively high doses. Morphine had a similar although weaker antihyperkinetic effect, whereas naloxone had no effect. Side effects of FK 33-824 included dizziness, heaviness in the extremities, slurred speech, and dryness of mouth. Morphine caused drowsiness, dizziness, ataxia, and nausea, and naloxone had no side effects. The results do not point to a primary role of enkephalin in the pathophysiology of TD, but enkephalin may interact with dopamine functions and potentiate some of the effects of neuroleptic drugs.