Delusional disorder (DD) is an underresearched psychotic disorder characterized by the presence of monosymptomatic delusions on a background of relatively well-preserved global functioning. Prominent hallucinations and significant affective symptoms are absent and response to treatment is poor due at least partially to a lack of adherence to antipsychotic (AP) medications. More recently, several studies have found a degree of cognitive impairment in DD patients, and affective symptoms are now more frequently reported. Treatment specifically addressing the different clinical domains of DD has not been sufficiently investigated and comprehensive treatment goals remain poorly defined. For this reason, the aim of this review is to summarize the current evidence on the following: efficacy and adverse events associated with antipsychotic medications, prediction of response, treatment of comorbidity, and prevention and promotion of mental wellbeing. This review focuses on optimizing treatment for this hard-to-treat condition and on discovering predictors of response. APs are the first-line treatment of DD. Second-generation APs are used most often because of their tolerability profiles. Evidence concerning pharmacological treatment is nevertheless scarce; clinical trial evidence of cognitive behavioral therapy effects is paradoxically more robust. Because of age-induced pharmacodynamic and pharmacokinetic alterations, adverse events of APs are most frequent in this population than in other psychotic conditions, perhaps because the onset of DD is usually in middle-to-old age. Some findings suggest that separately treating affective and cognitive comorbidity improves clinical outcomes. Targeting specific symptom domains and altering doses to suit the demands of age (and reproductive status in women) holds clinical promise. Recommendations are for a) combined psychosocial and pharmacologic intervention, b) health promotion and c) prevention of psychiatric comorbidity. Rehabilitative strategies that enhance recovery need further investigation. Research in this area needs to target specific, well-defined goals.
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