Depot neuroleptic maintenance treatment: clinical, pharmacological and neuropsychological aspects

Detta är en avhandling från Psychiatry

Sammanfattning: Neuroleptic maintenance treatment is effective to reduce the risk of further episodes of schizophrenia and other chronic psychoses, except affective. Lack of insight often lead to poor compliance to the prescripted medication. Then, neuroleptics might be given as depot injections. A group of chronic psychotic outpatients were assessed of clinical symptoms and side effects regularely during the three years. Rating scores were analysed in relation to drug doses (in chlorpromazine equivalents), drug plasma level and to performance in a small neuropsychological test battery (Tapping and Alternating tests, Digit Span test, Auditive and Visual Reaction Time tests and two self-rating scales). Of the 89 depot-treated patients 38 were not eligibble to enter the study. Outcome of the participating 51 patients and of the 38 non-eligible patients was examined in their hospital case records after 3 and 5 years. Only 18% of the 89 patients were stable after 5 years. Eight patients died at a median age of 47 years. Three of them committed suicide. Outcome was significantly worse for the non-eligible patient group (p<.01). The relapse risk was considerable even after 20 years duration of the illness. Relapse rate was high also in old patients. To reduce the relapse risk, depot neuroleptic doses should be tapered very slowly, maximum once a year and only in steps of 10-20% of the actual dose. The inter-individual variation of optimal doses and drug plasma levels are too large among the patients to define a "therapeutic window" of neuroleptic doses or plasma levels in maintenance treatment. The intraindividual variations of drug plasma levels were considerable and were not associated with side effect ratings. In a pilot study with a new dopamine D2 ligand, NCQ298, six neuroleptic-treated patients and six controls were examined using SPECT. The aim was to study if the ligand can be used to quantify D2-receptor occupancy. A significant difference in dopamine D2 receptor occupancy was obtained between neuroleptic-treated subjects and controls measured by SPECT, but the method must be more developed before it can be used as a standard method in finding the optimal neuroleptic dose. Simple motor tests can to some extent be used as an indicator of the rehabilitation potential of chronic psychotic patients. Subjects with prominent negative symptoms had more neuropsychological impairments than others. Patients with core schizophrenia had a markedly slower tapping rate in the right hand compared to the left, suggesting a more marked left-hemisphere disturbance. In patients with auditory hallucinationes tapping rates of especially the right hand correlated negatively to the intensity of hallucinations. Side effects, EPS, may slow performance of some motor tests (Finger Alternation) and also affect the reaction time.

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