Antipsychotic Medication-Induced Dysphoria: Its Meaning, Association with Typical vs. Atypical Medications and Impact on Adherence

Abstract

Antipsychotic medication-induced dysphoria is a relatively under-recognized and understudied effect of antipsychotic medication. Although the term is encountered in clinical practice and in the literature, there is no consensus regarding its exact meaning. This article is a narrative review of the literature on antipsychotic medication and dysphoria based on a pubmed database search. We found that antipsychotic medication-induced dysphoria is a term used to describe a negative and unpleasant affective state which seems to be more often associated with high potency first-generation antipsychotics and could potentially lead to medication non-adherence. Though it is plausible to expect antipsychotic medication-induced dysphoria to be related to extrapyramidal symptoms, most especially akathisia, the nature of the association remains unspecified. Furthermore, there is some evidence that dopamine blockade maybe involved in the pathogenesis of antipsychotic medication-induced dysphoria. However, the limited methods of the currently available studies make it impossible to conclusively address the question of which class of antipsychotic (first- or second-generation) has a higher prevalence and severity of the syndrome.

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder

“…In patients with a history of mixed episodes, prophylactic treatment after a manic or depressive episode should not only target the prevention of manic or depressive relapse, but also give special attention to mixed recurrences. This is particularly true if a prophylactic treatment has been chosen that might increase the risk of provoking a mixed state, e.g., long term antidepressant continuation after a depressive index episode (El-Mallakh et al 2008), or antipsychotic-induced dysphoria after a manic index episode (Wu and Okusaga 2015).…”

Side-effect monitoring of continuing LAI antipsychotic medication in UK adult mental health services

“…There are relatively few comparative data, but those that do exist suggest that dysphoria is up to three times more common with FGAs than with SGAs and is particularly associated with potent dopamine antagonists such as haloperidol. 25 The presence of dysphoria can be determined only through spontaneous patient reports and/or direct focussed questioning. We found that fewer than one in five patients had been asked about dysphoria in the last year, with no targeting of those patients prescribed LAI haloperidol.…”

<p>The modern perspective for long-acting injectables antipsychotics in the patient-centered care of schizophrenia</p>

“…A potentially useful factor associated with SGA LAIs in adherent patients (as well as in partially adherent and nonadherent patients) is reduction of treatment-related discomfort. FGAs are associated with negative subjective well-being and so-called neuroleptic dysphoria,76 both of which have been related to D 2 -receptor occupancy >70%. As discussed, both LAI and extended-release oral formulations are associated with more favorable pharmacokinetics,45 possibly implying that adequate plasma concentrations are more easily reached and that D 2 receptors are optimally occupied.…”