Anhedonia in depression: Implications in clinical practice and its association with patient prognosis
Anhedonia is a core symptom of major depressive disorder (MDD) that may respond poorly to commonly prescribed treatments.1 According to Professor Roger S McIntyre, Professor of Psychiatry and Pharmacology, University of Toronto, Canada, a deeper understanding of the distinct neurotransmitters and circuits underlying anhedonia and early data from the exploration of different treatment strategies offers new hope for patients and clinicians alike.
Anhedonia Defined as an impaired capacity to experience or anticipate pleasure1 Characterised by a loss of interest and/or pleasure in previously enjoyable activities2 | |
Anticipatory pleasure: “wanting” Relates to motivation | Consummatory pleasure: “liking” Corresponds with pleasure experience |
Anhedonia
Anhedonia is a common symptom of major depressive disorder (MDD), reported in ~75% of patients,1 and a frequent residual symptom in patients receiving antidepressant treatment.2 Anhedonia has been associated with poorer disease prognosis and suboptimal treatment response.1 Anhedonia has been shown to be significantly associated with higher rates of social withdrawal, social impairment, reactivity of mood, brooding about past events, and diurnal mood variation (all p<0.05) compared with those not reporting anhedonia3 and is also identified as having a major negative impact on self-reported psychosocial functioning.2
While ‘absence of pleasure’ is a broad definition of anhedonia, it has separate components: anticipatory anhedonia and consummatory anhedonia.4 Professor McIntyre said both components are usually present in people with depression, but that they are very different.
Anhedonia has been implicated in disturbances of the central dopaminergic mesolimbic and mesocortical reward circuit pathways.2 Unsatisfactory outcomes in anhedonia after treatment with selective serotonin reuptake inhibitors (SSRIs) suggest that neurotransmitters other than serotonin may be involved.2 Additional treatment strategies may be needed to address anhedonia and other symptoms that are predictors of poor treatment outcomes.5
Professor Roger McIntyre
Professor Roger McIntyre
Contributing factors
Loneliness has a significant effect on well-being, physical health, sleep, cognition and mental health.6 Professor McIntyre said this was the prelude coming into the COVID-19 pandemic and speculated this may be a factor that may predispose adverse mental health outcomes in younger people, who have a higher prevalence of loneliness than other age groups, and are also at risk of depression.7 A recent Italian study found that during the pandemic, the presence of anhedonia potentially predicts the severity of COVID-related MDD.8 Professor McIntyre speculated this could be due to stress on the reward system, with lockdowns and isolation preventing reward prediction.
Childhood trauma can lead to poor treatment outcomes in patients with major depression, with children who have been exposed to abuse at the age of 4–7 years 1.6 times less likely to achieve response or remission.9 In adulthood, people with depression who experienced childhood trauma may have high levels of anhedonia.10
Cannabis and benzodiazepine use may also exacerbate anhedonia.11,12
Treatment for anhedonia
Brintellix® (vortioxetine)13 is an antidepressant with a multimodal mechanism of action, with observed effects on cognition and anhedonia.1,2 Recent studies have shown that Brintellix® significantly improved symptoms of anhedonia at endpoint (as measured by SHAPS and MADRS anhedonia subscale scores vs baseline [p<0.0001]1, and MADRS anhedonia subscale scores vs placebo [5 mg: p=0.009; 10 mg: p<0.001; 15 mg: p=0.086; 20 mg: p<0.001]).2 A large meta-analysis examined the effect of Brintellix® on depressive symptoms in adults who had experienced childhood or recent trauma and found it to be effective in this group (as measured by MADRS; p<0.05 vs placebo for 10 mg and 20 mg, 5 mg and 15 mg not statistically significant).10
Considering the overall treatment of MDD, Professor McIntyre said a combined approach was often warranted, comprising of psychotherapy to target the psychological symptoms of depression, with pharmacotherapy being used for cognition and reward system symptoms.
Table 1. Adverse events occurring in ≥5% patients from a pool of 12 short-term studies13 | |||||
Adverse event, % | Vortioxetine 5 mg/day (n=1157) | Vortioxetine 10 mg/day (n=1042) | Vortioxetine 15 mg/day (n=449) | Vortioxetine 20 mg/day (n=812) | Placebo (n=1968) |
Nausea | 20.5 | 22.6 | 31.2 | 27.2 | 8.1 |
Diarrhoea | 6.6 | 5.4 | 9.4 | 5.5 | 5.5 |
Dry mouth | 6.4 | 5.5 | 6.0 | 6.5 | 5.6 |
Constipation | 3.4 | 3.6 | 5.6 | 4.4 | 2.9 |
Vomiting | 2.7 | 3.6 | 6.5 | 4.4 | 1.1 |
Nasopharyngitis | 5.3 | 4.0 | 3.6 | 4.9 | 3.9 |
Headache | 13.7 | 12.7 | 14.7 | 12.4 | 12.9 |
Dizziness | 5.5 | 5.2 | 7.1 | 6.3 | 5.3 |
| Before prescribing, please consult the Product Information for full tolerability and safety details.13 | |||||
MADRS: Montgomery-Åsberg Depression Rating Scale; SHAPS: Snaith-Hamilton Pleasure Scale
MADRS: Montgomery-Åsberg Depression Rating Scale; SHAPS: Snaith-Hamilton Pleasure Scale
Key points
- Anhedonia is a core symptom of major depressive disorder (MDD) that has a major negative impact on patients’ self-reported psychosocial functioning2
- Anhedonia may be amplified when a person has experienced past or recent trauma10
- Treatment outcomes with SSRIs for anhedonia are often unsatisfactory2
- Anhedonia has been implicated in disturbances of the central dopaminergic mesolimbic and mesocortical reward circuit pathways2