Can Crexont (Carbidopa/Levodopa) ER Cause Depression and Anxiety?
Yes, Carbidopa/Levodopa ER (including Crexont) can cause depression and anxiety as documented adverse effects. 1
Evidence from FDA Drug Label
The FDA drug label for Levodopa clearly lists psychiatric adverse reactions including:
- Depression with or without development of suicidal tendencies 1
- Anxiety 1
- Agitation 1
- Confusion 1
- Psychotic episodes including delusions and hallucinations 1
Mechanism of Action and Mood Effects
Levodopa therapy affects multiple neurotransmitter systems that can impact mood:
- Levodopa therapy can perturb the function of norepinephrine and serotonin systems, which are already affected by Parkinson's disease pathology 2
- These neurotransmitter disturbances have been intimately linked to the development and expression of anxiety and depression 2
- Long-term treatment with levodopa induces hypersecretion of insulin and growth hormone, which may contribute to metabolic changes affecting mood 3
Clinical Observations
Research has documented mood and anxiety fluctuations related to levodopa therapy:
- Studies have shown robust mood and anxiety effects that temporally parallel motor fluctuations during levodopa administration 4
- In a study of 50 Parkinson's patients, 22 developed depressive disorders during levodopa treatment 5
- Levodopa was not found to be an effective antidepressant agent, contrary to what might be expected given its dopaminergic effects 5
Risk Factors and Patterns
Several factors may influence the development of mood symptoms:
- Patients with a history of previous depressive episodes appear more susceptible to developing depression during levodopa therapy 5
- Anxiety symptoms may be more persistent than depressive symptoms, with studies showing that anxiety scores remained unchanged even when motor fluctuations improved with optimized levodopa delivery 6
- Higher levodopa doses have been associated with increased risk for various adverse effects, though the relationship is complex 3
Dopamine Agonist Withdrawal Syndrome
When adjusting levodopa therapy, clinicians should be aware of:
- Dopamine agonist withdrawal syndrome (DAWS) can occur when tapering dopamine medications 7
- DAWS symptoms include anxiety, panic attacks, dysphoria, depression, agitation, irritability, and suicidal ideation 7
- These symptoms can be refractory to levodopa and may persist for months to years in some patients 7
Clinical Management
For patients experiencing depression or anxiety while on Carbidopa/Levodopa:
- Monitor for psychiatric symptoms regularly during treatment 1
- Consider SSRIs for managing depression and anxiety in Parkinson's disease patients, as they appear to be relatively safe in this population 3
- Sertraline has been extensively studied and appears to have a lower risk of QTc prolongation compared to other SSRIs 3
- Avoid monoamine oxidase inhibitors and tricyclic antidepressants due to significant cardiovascular side effects 3
- For sleep disturbances associated with mood symptoms, consider cognitive behavioral therapy for insomnia before pharmacological interventions 3
Conclusion
The evidence clearly indicates that Carbidopa/Levodopa ER (Crexont) can cause depression and anxiety as documented adverse effects. These mood symptoms may result from the medication's impact on multiple neurotransmitter systems and can fluctuate with motor symptoms. Clinicians should monitor patients for these psychiatric symptoms and consider appropriate management strategies when they occur.