The aim of this randomized, single-blind trial is to evaluate the effectiveness and tolerability of high frequency or low frequency repetitive transcranial magnetic stimulation (rTMS) in patients with resistant bipolar depression. Patients will be assigned to receive either high or low frequency rTMS for 20 consecutive workdays (4 weeks). 10 Hz (high) frequency rTMS and 1 Hz (low) frequency rTMS will be given over the left or right dorsolateral prefrontal cortex (DLPFC), respectively. Patients will be assessed with several psychometric instruments at baseline, and at weeks 5 and 9.

Inclusion Criteria:

• Men or women aged 18 to 70 years
• Current major depressive episode (MDE) in the context of a bipolar disorder type I or II (according to the DSM-IV-TR) that has not improved after more than 2 adequate pharmacological trial(s) in the current episode (failure is defined as a lack of significant clinical improvement after the use of standard mood stabilizers, atypical antipsychotics and/or antidepressants given at their minimum effective dosage or higher for at least 4 weeks of duration)
• Baseline score ≥ 13 on the Quick Inventory of Depressive Symptomatology - Clinician-Administered (QIDS-C), i.e., a MDE of at least moderate intensity

Exclusion Criteria:

• Psychotic features in the current episode
• Lifetime history of a non-mood-related psychotic disorder
• Substance or alcohol abuse/dependence in the past 6 months
• Unstable medical disease (e.g., cardiovascular, renal)
• Presence of mood cycles of < 30 days duration
• Pregnancy and/or lactation
• Presence of a specific contraindication for rTMS (e.g., personal history of epilepsy or convulsion, metallic head implant)
• Hearing loss