Immediate Action Required: Stop Medications and Contact Prescriber Urgently
You must contact your prescriber immediately—worsening depression and dark thoughts while on Effexor (venlafaxine) and Abilify (aripiprazole) represent a psychiatric emergency requiring urgent medication reassessment. 1, 2
Critical Safety Concerns
Suicidality Risk with Antidepressants and Aripiprazole
Both venlafaxine and aripiprazole carry FDA warnings about increased suicidal thoughts and behaviors, particularly during the first few months of treatment or when doses are changed 1, 2.
The FDA specifically warns that patients must be monitored for emergence of agitation, irritability, unusual changes in behavior, anxiety, panic attacks, insomnia, hostility, aggressiveness, impulsivity, and worsening depression—all of which indicate the depression may be worsening 1, 2.
Families and caregivers should monitor for these symptoms on a day-to-day basis since changes may be abrupt, and such symptoms should be reported immediately to the prescriber 1, 2.
What You Should Do Right Now
Contact your prescriber today or go to an emergency department if you have thoughts of harming yourself 3, 1, 2.
Do not stop these medications abruptly without medical supervision, as sudden discontinuation of venlafaxine can cause severe withdrawal symptoms including anxiety, irritability, confusion, electric shock-like sensations, and worsening mood 2.
Your prescriber needs to evaluate whether to discontinue treatment, change medications, or adjust your therapeutic regimen 3, 2.
Expected Clinical Response Timeline
When Treatment Should Be Modified
Clinicians should assess patient status, therapeutic response, and adverse effects within 1 to 2 weeks of initiating antidepressant therapy 3.
If you do not have an adequate response within 6 to 8 weeks of starting therapy, treatment should be modified 3.
The risk for suicide attempts is greatest during the first 1 to 2 months of antidepressant treatment 3.
Your Current Situation
Feeling worse on these medications rather than better suggests treatment failure or adverse medication effects 3, 1, 2.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or who are experiencing emergent suicidality 2.
Medication-Specific Concerns
Aripiprazole (Abilify) Issues
Aripiprazole can cause anxiety, agitation, insomnia, and unusual changes in behavior—symptoms that overlap with worsening depression 1.
The FDA label specifically warns about clinical worsening of depression and suicide risk with aripiprazole, stating these symptoms may be associated with increased risk for suicidal thinking and behavior 1.
While aripiprazole augmentation has shown efficacy in some treatment-resistant depression cases 4, 5, it is not appropriate if it is causing worsening symptoms 1.
Venlafaxine (Effexor) Issues
Venlafaxine carries warnings about anxiety, insomnia, agitation, and worsening depression 2.
Serotonin syndrome is a potentially life-threatening risk with venlafaxine, particularly when combined with other serotonergic medications, and can present with mental status changes including agitation, hallucinations, and delirium 2.
Rare cases of venlafaxine-induced psychosis have been reported, particularly when combined with other dopaminergic medications 6.
Alternative Treatment Approaches
Switching Antidepressants
If initial therapy fails, switching to alternative second-generation antidepressants (sustained-release bupropion, sertraline, or extended-release venlafaxine) results in remission in approximately 1 in 4 patients 3.
No single second-generation antidepressant has superior efficacy over others, so selection should be based on adverse effect profiles, cost, and patient preferences 3.
Approximately 38% of patients do not achieve treatment response during 6 to 8 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 3.
Monitoring Requirements
Close monitoring should begin within 1 to 2 weeks after initiation of therapy and continue regularly 3.
Patients should be monitored for emergence of agitation, irritability, or unusual changes in behavior on a day-to-day basis 3, 1, 2.
Critical Pitfalls to Avoid
Never abruptly discontinue venlafaxine, as this can cause severe withdrawal symptoms including anxiety, confusion, electric shock-like sensations, and potentially worsening suicidal ideation 2.
Do not assume worsening symptoms are part of the underlying depression—they may represent medication-induced adverse effects requiring immediate intervention 1, 2.
Do not wait for a scheduled follow-up appointment—worsening depression and dark thoughts require urgent contact with your prescriber 3, 1, 2.