Can withdrawal from Quetiapine, Hydroxyzine, Venlafaxine, and Clonazepam cause a seizure?

Withdrawal from Multiple Psychiatric Medications and Seizure Risk

Yes, abrupt withdrawal from Clonazepam can cause seizures, and the combination of withdrawing from multiple psychiatric medications including Quetiapine, Hydroxyzine, Venlafaxine, and Clonazepam significantly increases this risk. The most concerning withdrawal is from Clonazepam (a benzodiazepine), which has well-documented seizure risk upon discontinuation.

Seizure Risk by Medication

Clonazepam (Benzodiazepine)

• Highest seizure risk of the medications listed
• Benzodiazepine withdrawal can cause seizures even after short-term use (less than 15 days) and at therapeutic doses 1
• Seizures are typically grand mal and can range from a single episode to severe cases resulting in coma or death 1
• Prolonged benzodiazepine use leads to withdrawal symptoms including anxiety, agitation, tremors, headaches, sweating, insomnia, nausea, vomiting, myoclonus, muscle cramps, hyperactive delirium, and seizures 2

Venlafaxine

• Can cause seizures even at therapeutic doses
• Case reports document complex partial seizures at low therapeutic doses 3
• Withdrawal can contribute to seizure risk, particularly in combination with other medications 4

Quetiapine

• Delayed seizure onset has been reported in overdose cases 5
• While antipsychotics generally have a low seizure risk (usually <1%) at therapeutic doses, withdrawal may lower seizure threshold 2
• Combined with other medications, risk increases 4

Hydroxyzine

• Lowest seizure risk of the medications listed
• No strong evidence for seizures with withdrawal
• However, contributes to overall CNS depression when combined with other medications 2

Risk Factors for Withdrawal Seizures

1. Abrupt discontinuation - particularly concerning with benzodiazepines
2. Duration of treatment - longer use increases dependence and withdrawal severity
3. Multiple medication withdrawal simultaneously - compounds risk significantly
4. High doses - higher doses increase risk but seizures can occur at therapeutic doses
5. Additional factors - history of seizures, alcohol use, electrolyte abnormalities 6

Management Recommendations

1. Never abruptly discontinue these medications, especially Clonazepam

   • Taper benzodiazepines gradually, reducing dose by 25% every 1-2 weeks 2
   • For long-term benzodiazepine users, even slower tapering may be necessary 2

2. Sequential rather than simultaneous tapering

   • Taper opioids first if applicable, then benzodiazepines 2
   • For these specific medications, taper in this order:
     • Venlafaxine
     • Quetiapine
     • Hydroxyzine
     • Clonazepam (last and most gradually)

3. Monitoring during withdrawal

   • Watch for early signs of withdrawal: anxiety, irritability, insomnia, tremors
   • These may precede seizures and indicate need for slowing the taper

4. Extended tapering for Clonazepam

   • Withdrawal should extend over more than one month for most cases 2
   • Consider re-escalating dose if withdrawal symptoms become severe

Special Considerations

• Antipsychotic withdrawal (Quetiapine): Gradual withdrawal recommended to minimize discontinuation effects including dyskinesias, parkinsonian symptoms, dystonias, and neuroleptic malignant syndrome 2

• Venlafaxine withdrawal: Can cause its own withdrawal syndrome that may complicate the overall picture 4

• Combined CNS depressant effects: All four medications have CNS depressant effects that may have been balancing each other; removing them can unmask excitatory rebound 2

Emergency Management if Seizure Occurs

If seizures occur during withdrawal:

1. Stabilize patient
2. Consider reinstating the benzodiazepine at previous dose
3. Implement a more gradual tapering schedule
4. Consider anticonvulsant coverage during the remainder of the taper

The risk of withdrawal seizures is real and potentially life-threatening. Proper tapering under medical supervision is essential when discontinuing these medications, particularly when multiple CNS-active medications are involved.