Atypical neuroleptics that block serotonin 2A (5-HT 2A) and dopamine 2 (D2) receptors have been shown to possess efficacious antipsychotic activity. We assessed the efficacy of the addition of the 5-HT 2A/2C and α2 antagonist mianserin to ongoing haloperidol treatment in chronically hospitalized (> 10 years) drug-resistant schizophrenic patients (N = 12). The patients were assessed at baseline and every three months for one year with the Brief Psychiatric Rating Scale and the Clinical Global Impression. Results showed a significant (but < 10%) improvement in the core symptoms of schizophrenia; however, only the reduction (by 43%) in anxiety was clinically relevant (P < 0.0001). The beneficial effect of mianserin may be related to the combined blockade of 5-HT 2A and histamine (H1) receptors.

Two clinical observations of mianserin abuse by psychiatric out-patients are described. A previous history of substance dependence was found in both cases. Mianserin should be used with caution in predisposed patients, before further studies on the subject are carried out.

In patients with chronic idiopathic pain disorders we have analysed the construct validity of the Melancholia Scale as compared to the results with the scale in primary depression. The patients (n= 253) were treated in a placebo controlled trial with either clomipramine or mianserin independently of the Melancholia score. The construct validity of the Melancholia Scale was further analysed by the testing of the intensity model of depression versus anxiety using the Beck Depression Inventory, the Hamilton Anxiety Scale, the Spielberger State-Trait Anxiety Scale, and the Melancholia Scale. The construct validity in terms of scale homogeneity was analysed by Loevinger coefficients which can be considered as a latent structure evaluation. The Melancholia Scale showed acceptable homogeneity, while the Hamilton Anxiety Scale lacked sufficient homogeneity. In total, 33% of the patients had a score of 10 or more on the Melancholia Scale (corresponding to 13 or more on the Hamilton Depression Scale). The predictive validity of the Melancholia Scale was evaluated using active treatment versus placebo response after 6 weeks of therapy. It was shown that in patients with a Melancholia Scale score of 10 or more (corresponding to “less than major depression”) 72% had full recovery when treated with clomipramine, while 36% of the placebo treated patients obtained a full recovery (P≤0.05). The patients treated with mianserin obtained a full recovery in 52%. The group of patients with a Melancholia Scale score of 10 or more scored higher also on the anxiety scales indicating that the relation between depression and anxiety is a matter of severity. The depressed patients had significantly lower imipramine binding sites than the non-depressed patients.

Several well-known observer scales, including the Hamilton Depression Scale (HAM-D), Montgomery-Åsberg Scale (MADRS), Major Depression Rating Scale (MDS), Melancholia Scale (MES), and Inventory for Depressive Symptomatology (IDS) used for measuring severity of depressive states have been compared by their responsiveness in an open trial including patients treated with a combination of citalopram and mianserin. The patients fulfilled the Diagnostic and Statistical Manual (DSM)-IV criteria for major depressive episode, and all scored 18 or more on the HAM-D before treatment. Onset of antidepressant action was defined as an improvement of rating scale scores of 25% or more of pre-treatment scores. A response to treatment was defined as a reduction of 50% or more on the pre-treatment scores. The results showed that the number of treatment days until improvement was 11 to 13 with no difference between the scales. The days until response were between 18 and 21 with no difference between the scales. In conclusion, the depression scales were found to be equal in their ability to detect changes in depressive symptoms during treatment. The mean of days to response was 19 for the combination of citalopram and mianserin. This is similar to the response for the combination of fluoxetine and pinolol.