Can Ambien Cause Depressive Symptoms?
Yes, Ambien (zolpidem) can cause or worsen depressive symptoms, including continuing or aggravated depression, as documented in FDA labeling and clinical trials. 1
Evidence from FDA Drug Labeling
The FDA-approved prescribing information for zolpidem explicitly documents depression as an adverse reaction:
- In clinical trials with SSRI-treated patients given zolpidem, 4 of 7 discontinuations during double-blind treatment were associated with "continuing or aggravated depression" and manic reaction 1
- Depression was reported in 2% of patients in long-term trials (28-35 nights) at a greater frequency than placebo 1
- The FDA labeling includes a specific warning about "Abnormal Thinking and Behavior Changes" as a serious adverse reaction requiring monitoring 1
Clinical Context and Mechanism
While zolpidem may have some neurochemical effects on GABA systems that could theoretically benefit depression when combined with SSRIs 2, the clinical reality is more concerning:
- Zolpidem users in psychiatric treatment for insomnia demonstrate severe depressive symptoms that are significantly associated with severe dependence on the medication 3
- The drug can produce mood disturbances and behavioral changes that manifest as worsening depression 1
- Withdrawal from zolpidem can cause severe symptoms requiring hospitalization, even at relatively low doses 4
Risk Factors and Monitoring
Patients at highest risk for depressive symptoms with zolpidem include:
- Those already taking SSRIs or being treated for depression 1
- Individuals using high doses or long-term therapy (>3 months) 3
- Patients with pre-existing mood disorders 1
Clinical Recommendations
When prescribing zolpidem to patients with depression or at risk for mood disturbances:
- Monitor closely for continuing or worsening depressive symptoms, particularly in the first weeks of treatment 1
- Be especially vigilant in patients already on SSRIs, as the combination has been specifically associated with aggravated depression 1
- Consider that behavioral therapy (BT) produces larger improvements in anxiety symptoms compared to zolpidem and may be preferable for patients with mood concerns 5
- Educate patients about the potential for dependency and withdrawal symptoms, which can include severe mood disturbances 4
- Avoid abrupt discontinuation; taper carefully if stopping the medication 6, 4
Important Caveats
The relationship between zolpidem and depression is complex—while the drug can cause or worsen depression, it may also improve daytime mood symptoms indirectly by treating insomnia 5. However, the documented cases of aggravated depression in clinical trials and the FDA's explicit warnings make this a real and clinically significant risk that requires active monitoring 1.