Major depressive disorder (MDD) develops in 15-40% of patients treated with interferon-alpha. Usually, depression appears within 2-3 months after interferon’s introduction and stops after interferon therapy’s end.
Interferon-induced depression (IFN-MDD) is manifested as:
- fatigue and malaise;
- anhedonia, depressed mood;
- irritability, anxiety;
- Social exclusion;
- poor focus;
- sleep disturbances;
- personality changes and suicidal ideation.
Similar processes accompany both conventional depression and IFN-BDR:
- Elevated levels of many inflammatory cytokines, which may be a consequence of psychosocial stress.
- Interferon-alpha (IFN-α) and other cytokines can suppress the serotonin and dopamine systems.
- In addition to synthesis in the brain, peripheral cytokines, and IFN-α can enter the central nervous system.
- Systemic administration of IFN-α and other cytokines may decrease motivation and cause anhedonia.
- The introduction of IFN-α can affect the function of the frontal lobe and the anterior cingulate gyrus, which may contribute to depression.
- 79-85% of patients with IFN-MDD respond to effective treatments for common depression, ranging from selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants to electroconvulsive therapy.
Prevention of depression during treatment with interferon: antidepressants
Depression is associated with increased psychosocial stress, the postpartum period, hypothyroidism, circadian rhythm disturbances, cerebrovascular disease, and administration of interferon-α and other inflammatory cytokines. Thus, one approach to preventing depression may be to avoid these triggers. However, this is often not feasible.
Thus, it is impossible to avoid the introduction of interferon in certain serious diseases. For example, interferon is used to treat chronic hepatitis C, which affects nearly 2% of the US population and about 170 million people worldwide. Untreated chronic hepatitis C can lead to cirrhosis, hepatocellular carcinoma, and liver failure. Hepatitis C deaths outnumber AIDS deaths. Approximately 10,000 patients a year die from hepatitis C in the United States.
Interferon is the only FDA-approved drug for the treatment of hepatitis C. Although interferon treatment can cause depression, increasing the risk of suicide, reducing the dose of interferon or stopping treatment is also life-threatening, increasing the risk of viral relapse and reducing the quality of life.
Several studies have shown that selective serotonin reuptake inhibitors (SSRIs) prevent interferon depression. In these studies, non-depressed participants took prophylactic SSRIs before initiation of interferon-alpha treatment:
- A randomized placebo-controlled trial in patients with metastatic melanoma who received very high doses of intravenous IFN-alpha showed that SSRIs significantly reduced the risk of depression: 11% in the SSRI group versus 45% in the control group.
- In three other studies of patients with chronic hepatitis C, only 9% of patients treated prophylactically with SSRIs developed interferon depression despite having a history of mood disorders.
The other two studies in patients with hepatitis C did not confirm the prophylactic efficacy of SSRIs against MDD-INF. However, in these patients, SSRIs reduced the severity of depression.
IFN-RDD prophylaxis with SSRIs is most effective in patients already depressed before interferon treatment and in patients in remission with a history of depression. For these patients, SSRIs may prevent further worsening of depressive symptoms or relapse of depression. Scientists at the Western Psychiatric Institute and Clinic in the United States have recently confirmed this. Their study involved 31 patients who had not been depressed within six months before starting IFN-α therapy but had a history of depression. Ten patients were stably taking SSRIs. In the SSRI group, IFN-RDD developed only in 20% of patients, and in the group without antidepressants, in 48%. Similar results were shown by a meta-analysis involving 196 patients: 97 in the SSRI group and 99 in the control group. SSRIs before IFN-α treatment significantly reduced the incidence of interferon depression: 15% vs. 36%.
Prevention of Depression: Lifestyle Factors
The risk of depression during IFN-α treatment increases:
- Poor sleep quality or insomnia. Restoring normal sleep is essential to prevent depression.
- Old age. The inflammatory cytokine IL-6 is elevated in older people, and high IL-6 before IFN-α therapy is associated with subsequent IFN-RDD. To prevent depression, elevated IL-6 levels can be reduced through diet and exercise.
- Social isolation and neuroticism. Psychological and social support may help prevent IFN-RDD.
- Hyperactive stress response of the hypothalamic-pituitary-adrenal axis. Antidepressants can lessen this reaction.
- Genetic disorders in the serotonergic system. Prophylactic antidepressants may also be helpful in this group of patients.
Conclusion
Prophylactic SSRIs can halve the incidence of interferon-induced depression. SSRIs will be especially useful in patients with a history of depression or existing depressive symptoms before starting interferon treatment. SSRIs prevent the recurrence of depression and counter the worsening of depressive symptoms. However, despite taking antidepressants, approximately 15-20% of patients may still develop interferon depression. Therefore, it is also important to reduce other risk factors for MDD: improve sleep quality, reduce elevated levels of the inflammatory cytokine IL-6 through diet and exercise, and provide patients with psychological and social support.
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Reference
Major depression during interferon-α treatment: vulnerability and prevention
