Treating Motivational and Consummatory Aspects of Anhedonia

Anhedonia is a devastating psychiatric symptom that is found across a variety of psychiatric disorders (1). Commonly defined as a loss of motivation, interest, or capacity to derive pleasure from previously enjoyed activities, anhedonia is one of the rare transdiagnostic symptoms that spans the internalizing, externalizing, and thought-disorder dimensions of the hierarchical structure underlying psychiatric disorders (2–5). Despite its prevalence, treatments for anhedonia have lagged behind other areas, and the development of tools for addressing anhedonia represents an area of urgent clinical need.

Varieties of Anhedonic Presentation

Growing evidence has suggested that anhedonia is a multifaceted symptom domain, and that various components of anhedonia and other symptoms may interact to drive clinical presentation. In recent decades, a consensus has emerged to separate loss of interest or motivation (i.e., motivational anhedonia) from the capacity to enjoy rewards (i.e., consummatory anhedonia) (6). Importantly, these dimensions are neither independent nor mutually exclusive. Indeed, repeated failure to derive pleasure from previously enjoyed activities can easily blunt subsequent motivation, and a loss of motivation can lead to an increase in reporting of low enjoyment, because individuals will often conclude that their lack of interest is likely due to a low expectation of reward (7).

In individuals experiencing posttraumatic stress disorder (PTSD), both motivational and consummatory aspects of anhedonia may occur (8, 9). In the aftermath of trauma, motivational and consummatory anhedonia may be closely related to—and difficult to distinguish from—behavioral avoidance and emotional numbing, respectively (9, 10). Ultimately, lower level, more specific analysis may be required to truly distinguish the varieties of anhedonia experienced in PTSD. Indeed, the division between motivational and consummatory aspects of reward has long been observed in preclinical studies, in which substantial evidence has accumulated to suggest that these processes are neurobiologically dissociable through manipulations of the mesolimbic dopamine and mu-opioid systems, respectively (11, 12). Recently, human functional MRI research (13) has also suggested that neural population coding of motivational and pleasurable aspects of reward are similarly distinct and appear to reflect a dichotomy similar to that between dopaminergic and opioidergic circuitry. Application of this research to clinical populations, however, remains in the early stages.

Treatment Hierarchies for Anhedonic Presentation

Treatment of Underlying Primary Issues

In addition to subtypes of anhedonia presentation, the widespread prevalence of anhedonia suggests that, in many cases, it is likely a consequence of other psychiatric symptoms and syndromes (i.e., “secondary anhedonia”), rather than a primary pathology in its own right. Examples of secondary anhedonia can include the low levels of enjoyment and interest reported during early stages of sobriety; a high propensity toward dissociative states that limit capacity for pleasure; and cognitive impairments that may impede the necessary planning and coordination for engaging in social activities. Pervasive anxiety resulting in limited activities and social isolation can also lead to reported loss of enjoyment. Such etiologic considerations are important for treatment customization. In some cases, secondary anhedonia may spontaneously remit if the primary issues are addressed.

Empirically Supported Behavioral Interventions for Anhedonia

Although treatment options for anhedonia have lagged behind those for other dimensions of internalizing psychopathology, evidence supporting several behavioral and pharmaceutical interventions has emerged. On the behavioral side, behavioral activation (14, 15) and positive affect therapy (16, 17) have shown evidence in enhancing behavioral engagement and reducing avoidance. Both therapies are modular and primarily target aspects of motivational impairment rather than consummatory anhedonia. Indeed, to a large extent, both therapies operate on the underlying assumption that the capacity to experience pleasure is generally intact; the primary goal of treatment is therefore to facilitate greater opportunity for engaging in pleasurable activities. This goal is often accomplished by helping patients to identify activities that provide pleasure or a sense of achievement (i.e., mastery), to prioritize these activities in daily routines, and to identify and problem-solve around barriers to these activities. For consummatory anhedonia, mindfulness-based interventions designed to focus attention on savoring rewards have been developed in the context of substance use disorders (18) and may offer strategies for enhancing pleasure in other disorders as well.

Empirically Supported Pharmacologic Interventions for Anhedonia

For pharmacologic interventions, treatment using dopaminergic agents has been found to improve symptoms of low motivation and anhedonia-associated fatigue in several studies (19, 20), consistent with a wealth of preclinical and human experimental data suggesting that enhancement of dopaminergic tone may result in greater motivated behavior (21–23). Stimulants carry noteworthy side effects, however, including suppressed appetite, weight loss, hypertension, cardiac arrythmias, and potential for abuse. Despite these risks, more research into the possible application of stimulants to treat the motivational aspects of anhedonia is warranted. Indeed, a recent meta-analysis (19) evaluating the use of several agents at different dosages found that psychostimulants were generally efficacious, and their use as an adjunctive agent or monotherapy represented an understudied area.

In addition to psychostimulants, some evidence supports dopamine-replacement therapy for certain presentations of anhedonia. In particular, a growing body of evidence suggests that chronic peripheral inflammation may blunt dopamine synthesis capacity, possibly contributing to symptoms of fatigue, low motivation, and psychomotor slowing (24, 25). Initial evidence (26) suggests that administration of levodopa, a dopamine precursor commonly used to treat Parkinson’s disease, may benefit patients who show low motivation and elevated inflammation. Finally, the fast-acting antidepressant ketamine has shown some initial promise in addressing multiple aspects of anhedonia, including incapacity for pleasure (27, 28).

Summary

Taken together, anhedonia is a pervasive and challenging symptom to treat. In many cases, anhedonia may be secondary to other factors, and may improve with targeting of the underlying issues. In cases of primary anhedonia, several behavioral interventions with strong empirical support exist, although they primarily focus on motivational impairments. Dopaminergic therapies may also help patients with low motivation, although more research is needed. Finally, some initial evidence suggests that ketamine may emerge as a successful intervention strategy for primary consummatory anhedonia.