Patient X is a 32-year-old male who presented with chronic obsessive-compulsive disorder with somatic fixation, depression, and generalized anxiety disorder. Patient X was treated with pharmacological interventions and psychotherapy for 50 months before beginning ketamine/TMS treatment. During this initial treatment phase, Patient X’s symptoms did not respond to treatment with the mood stabilizers (olanzapine and valproic acid), antidepressants (desvenlafaxine, sertraline, and fluvoxamine), anti-anxiety medication (chlorazepate), psychostimulants (lis-dexamphetamine, and methylphenidate), gabapentin, or conventional psychotherapy. Before beginning ketamine/TMS treatment, Patient X had been coincidentally referred to a licensed psychologist for a comprehensive pretreatment assessment of symptomatology. The assessment included the Beck Depression Inventory-2 (BDI-II), the Beck Anxiety Inventory (BAI), the Beck Hopelessness Scale (BHS), and the Personality Assessment Inventory (PAI), which includes subscales measuring a variety of psychopathology domains. PAI subscale scores greater than 70 indicate clinically significant difficulties. At the pretreatment assessment, Patient X exhibited severe levels of depression (BDI-II = 48) in terms of cognitions (PAI DEP-C = 81), affect (PAI DEP-A = 77), and appraisals of hopelessness (BHS = 18). In addition, Patient-X reported severe anxiety (BAI = 52). Related to these symptoms, Patient X reported a high degree of suicidal ideation (PAI SUI = 89). Patient X also demonstrated clinically significant levels of obsessive-compulsive symptoms (PAI ARD-O = 78). The OCD symptoms included engaging in behavioral rituals to decrease anxiety, fear of losing control of impulses and handling contaminated objects, a heightened need for order, high anxiety in messy or disordered environments, being excessively detailed and pedantic, a strong need to control his feelings and thoughts, and overarching perfectionism.

Prior to beginning combined treatment, Patient-X was given 2 days of rTMS pretreatment (4 treatments per day of 30 minutes each with 45 minutes of rest between treatments). Combined ketamine/TMS treatment began the following day and continued twice per week for 10 weeks. Combined treatment consisted of 50 minutes of 1Hz continuous TMS with an intravenous ketamine infusion administered concurrent to and bracketed within the middle 40 minutes of TMS, resulting in 5 minutes of TMS pre and post infusion. The dosage of infused ketamine increased gradually from 40 mg at the first treatment to a peak of 425 mg at the 12th treatment, and tapered down to 225 mg at the last treatment. The dose increases occurred in order to assist the patient in reaching a mildly dissociated and cataleptic state. I hypothesized that greater dosages were needed until central nervous system function reached a point of maximal health. I defined this point as when both the patient and a close family member rated the patient’s functioning as normal. Once normal functioning was achieved, I began to taper the dosage. During combined treatment, the TMS head coil (manufactured by Neotonus) was positioned at the midline (Fz on 10/20 positioning system) of the anterior scalp to achieve maximal stimulation of the medial prefrontal area that overlays the anterior cingulate, a region implicated in depression (Gross et al. 2007). TMS treatments were administered at 115% of motor threshold (threshold of comfort for this patient) at 1Hz continuous pulsation given that these settings were within safety guidelines and consistent with my usual method. Using this method, I hypothesized that the dissociative effects of ketamine along with TMS activation of the anterior cingulate would help reestablish normal oscillatory rhythms in this region, leading to a decrease in depression and OCD symptoms.

After 8 twice-weekly treatments, Patient X began to report improvements in mood that increased throughout treatment. At post-treatment, Patient X was again evaluated, by the same licensed psychologist for comprehensive assessment. At this assessment, Patient X reported greatly decreased levels of depression (BDI-II = 13) in terms of cognitions (PAI DEP-C = 61), affect (PAI DEP-A = 66), and appraisals of hopelessness (BHS = 4). In addition, Patient X reported reduced anxiety (BAI = 24) and no ongoing evidence of suicidal ideation (PAI SUI = 51). However, Patient X’s obsessive-compulsive symptoms remained elevated (PAI ARD-O = 84).