Biological interventions in the treatment of paranoid personality disorder are limited to the use of drugs. Although the psychotic process in a delusional paranoid patient may be effectively treated by antipsychotic medication, such is not the case in paranoid personality disorder. The increase in suspiciousness and guarded behavior that has been observed after cocaine infusion, similar to the early stages of amphetamine-induced psychosis, has led to speculations that dopamine metabolism may be the operative mechanism. Attempts to treat these symptoms with a combination of phenothiazine and lithium have proved unsuccessful. Slight improvement has been noted in some cases with low-dose antipsychotics, especially thioridazine or haloperidol, but for all practical purposes, the role of drugs with such patients is more or less limited to modifying specific target symptoms that may occur because of the failure of characterological defenses. Thus, at certain times in the course of treatment, limited use of minor tranquilizers for the treatment of anxiety, or of tricyclic or antiserotonergic antidepressants or monoamine oxidase inhibitors for the treatment of phobic anxieties or depression, might be indicated. Benzodiazepines may have limited antiaggressive effects, and recent evidence suggests that fluoxetine may be useful in controlling irritability and aggressive behavior.

One difficulty in the management of paranoid patients is that they are often extremely resistant to taking medications of any kind, often seeing them in terms of issues of control, powerlessness, and loss of autonomy. In the face of such resistance, the clinician often must make a difficult decision as to whether the potential advantages of the pharmacotherapy outweigh the consequences of insisting on the medication and the possible harm to the therapeutic relationship and process. Because of the nature of the symptomatology, medication is often not effective, so that gains from insisting on the patient’s taking the medication can be minor, whereas the negative implications for the patient’s relationship with the therapist and their influence on the outcome of the therapy may prove to be major.