Can Transcranial Magnetic Stimulation (TMS) be used to treat Obsessive-Compulsive Disorder (OCD) in a patient with a remote history of seizures and currently taking clomipramine (tricyclic antidepressant)?

TMS Use in OCD with Remote Seizure History and Concurrent Clomipramine

TMS can be used in this patient, but requires careful risk-benefit assessment given the dual seizure risk from both remote seizure history and concurrent clomipramine therapy, which lowers seizure threshold. The overall seizure risk with TMS remains <1%, and the potential benefits of treating refractory OCD may outweigh the risks, particularly since the last seizure was over 20 years ago and the patient is not currently on antiepileptic medications 1.

Risk Assessment Framework

Seizure Risk Factors Present

• Remote seizure history (>20 years): TMS has been successfully used in patients with epilepsy and prior seizure history, though this increases baseline risk 1
• Clomipramine therapy: This tricyclic antidepressant has a documented 0.4% incidence of seizures and lowers seizure threshold 2, 3
• Combined risk: The interaction between clomipramine's seizure-lowering effects and TMS-induced cortical excitation creates additive risk, though the absolute risk remains relatively low 1, 4

Mitigating Factors

• The patient is not currently on antiepileptic medications, suggesting seizure disorder is well-controlled or resolved 1
• Over 20 years seizure-free represents substantial time without active seizure activity 1
• TMS-related seizures, when they occur, are typically self-limiting and treatment recommendations are supportive 1

Clinical Context for TMS Consideration

This patient appears to have treatment-resistant OCD given they are already on clomipramine, which is reserved as second- or third-line therapy after SSRI failure 5. According to treatment algorithms, deep rTMS is specifically indicated for patients with inadequate response to standard treatments 6.

Treatment Hierarchy Position

• Clomipramine is used after at least one adequate SSRI trial at maximum doses for 8-12 weeks has failed 5
• Deep rTMS is FDA-approved for treatment-resistant OCD and appears in treatment algorithms alongside clomipramine for refractory cases 6
• TMS demonstrates moderate therapeutic effect (effect size = 0.65) with 3-fold increased likelihood of treatment response compared to sham 7

Safety Considerations Specific to This Case

Clomipramine-TMS Interaction

• Major concern: Clomipramine increases seizure risk through lowering seizure threshold, and combining with TMS creates additive cortical excitation 2, 3
• Cardiotoxicity monitoring: Clomipramine has potential for cardiac conduction impairment; ensure baseline ECG is normal before adding TMS 2
• Serotonin syndrome risk: While not directly related to seizures, monitor for serotonergic symptoms given clomipramine's potent serotonergic effects 6

Protocol Selection Matters

• The FDA-approved bilateral DMPFC protocol for OCD uses 20-Hz stimulation, which has documented seizure cases even in otherwise healthy patients 4
• Longer individual TMS sessions and fewer overall sessions predicted greater clinical improvement in meta-analysis 7
• Consider starting with conservative parameters and gradually increasing intensity while monitoring for any concerning symptoms 1

Practical Implementation Strategy

Pre-Treatment Requirements

• Neurology consultation: Obtain clearance from neurology given remote seizure history, particularly to assess seizure etiology and recurrence risk 1
• Baseline ECG: Rule out cardiac conduction abnormalities given clomipramine's cardiotoxic potential 2
• Informed consent: Explicitly discuss the <1% overall seizure risk, which may be higher in this specific case due to combined risk factors 1, 4

Monitoring During Treatment

• Session-by-session assessment: Monitor for any prodromal seizure symptoms, changes in consciousness, or unusual sensations 1, 4
• Avoid additional risk factors: Ensure adequate sleep and avoid alcohol, both of which increase seizure risk with TMS 1
• Emergency preparedness: Have seizure management protocols readily available, though most TMS-induced seizures are self-limiting 1

Risk-Benefit Calculation

• Potential benefit: Moderate effect size for OCD symptom reduction, particularly important given treatment resistance 7
• Absolute risk: Even with combined risk factors, seizure incidence likely remains in low single digits percentage 1
• Alternative options: If TMS is declined, remaining options include antipsychotic augmentation (risperidone/aripiprazole), glutamatergic agents (N-acetylcysteine, memantine), or intensive residential treatment 6, 5

Common Pitfalls to Avoid

• Underestimating combined risk: Don't dismiss the additive seizure risk from clomipramine plus TMS; this requires explicit discussion 2, 1
• Proceeding without neurology input: Given documented seizure history, neurology consultation provides essential risk stratification 1
• Ignoring sleep deprivation: Sleep deprivation significantly increases TMS seizure risk; ensure patient maintains adequate sleep hygiene 1
• Assuming all TMS protocols are equal: The 20-Hz bilateral DMPFC protocol has specific seizure case reports; consider this when selecting parameters 4