In an older adult with chronic hepatitis C and normal liver function who is currently manic (no depression) and is on multiple serotonergic agents, should I restart an SSRI?

Do Not Restart the SSRI in This Manic Patient

You should not restart the SSRI while this patient is actively manic, as SSRIs are contraindicated in patients with current mania or suspected bipolar disorder due to the significant risk of worsening mania or triggering a full manic episode. 1

Primary Concern: SSRI-Induced Mania Risk

• SSRIs should be avoided in patients with a history of bipolar depression or current manic symptoms due to the risk of precipitating or exacerbating mania. 1
• The American Academy of Child and Adolescent Psychiatry guidelines note that antidepressants may destabilize mood or incite manic episodes, and caution that manic symptoms associated with SSRIs may represent unmasking of bipolar disorder. 1
• Even without a formal bipolar diagnosis, the presence of current manic symptoms is a contraindication to SSRI initiation or reinitiation. 1

Additional Risk: Serotonin Syndrome

• This patient is already on multiple serotonergic agents, which substantially increases the risk of serotonin syndrome if you add an SSRI. 1
• Serotonin syndrome can present with mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis). 1
• Advanced cases can progress to fever, seizures, arrhythmias, unconsciousness, and death. 1
• The risk is particularly elevated when combining two or more non-MAOI serotonergic drugs, requiring extreme caution even when starting at low doses. 1

Hepatitis C Context

• While the patient has normal liver function tests, interferon-based therapy for hepatitis C (if previously used) is known to induce or exacerbate psychiatric symptoms including depression, mania, and hypomania. 2, 3
• Patients with manic traits who undergo interferon therapy have significantly higher rates of adverse psychiatric events (73% versus 30% in controls). 4
• If depression develops during hepatitis C treatment, antidepressants can be used, but only after the manic symptoms have fully resolved and ideally after psychiatric consultation. 1

Recommended Management Algorithm

1. Immediately refer to psychiatry for formal evaluation of possible bipolar disorder versus substance-induced mania versus behavioral activation. 1

2. Do not restart the SSRI until psychiatric evaluation is complete and manic symptoms have resolved. 1

3. Review and potentially reduce or discontinue other serotonergic agents currently being used to minimize polypharmacy risks. 1

4. If bipolar disorder is confirmed, the patient will require mood stabilizer therapy (lithium, valproate, or atypical antipsychotics) before any consideration of antidepressant use. 1

5. If depression recurs after mania resolves, SSRIs may only be considered as adjuncts while the patient is maintained on at least one mood stabilizer, with close monitoring for mood destabilization. 1

Critical Pitfalls to Avoid

• Do not assume this is simple "behavioral activation" from previous SSRI use—true mania typically appears later in treatment and persists after SSRI discontinuation, requiring active pharmacological intervention rather than simple dose reduction. 1
• Do not restart the SSRI "at a lower dose" thinking this will be safer—the risk of mania is not clearly dose-dependent, and any SSRI exposure in an actively manic patient is contraindicated. 1
• Do not delay psychiatric referral while "monitoring"—morbidity and mortality risks increase with untreated mania, and the patient requires expert evaluation now. 1