Use of Transcranial Magnetic Stimulation for the Treatment of PTSD

I Got Your Six, by MSG Martin J. Cervantez, courtesy of the Army Art Collection, US Army Center of Military History

Posttraumatic stress disorder (PTSD) is a complex illness that rarely occurs in isolation from other psychiatric morbidities, and often fails to remit with standard therapies. Traditionally, PTSD is treated with psychotherapy and/or pharmacotherapy, with treatment choices often based on availability, patient preference, and patient tolerance. One of the more commonly recommended psychotherapy treatment modalities is exposure-based therapy, where a patient recalls traumatic events, usually with some form of relaxation, with the hope of inducing extinction of the anxiety response to the stimulus [1]. In addition to treatment with psychotherapy, pharmacotherapy is also commonly administered, despite potentially adverse side effects and the risk of polypharmacy. Many patients are prescribed psychotropics to ameliorate symptoms, particularly if PTSD exists with other comorbid conditions. While psychotherapy and pharmacology may have utility for many patients, their limited efficacy promotes the need for novel treatment options. One possible alternative treatment option is transcranial magnetic stimulation (TMS) , which is a noninvasive brain stimulation technique that has a broad range of therapeutic capabilities.

11.1 Care Presentation/History

A 35-year-old African American male with a history of recurrent depression since age 14 and PTSD symptoms resulting from two deployments to Afghanistan, self-referred for repetitive transcranial magnetic stimulation (rTMS) after hearing about the technology on the radio and investigating its features online. His depressive symptoms were characterized by depressed mood, anhedonia, low energy, fragmented sleep, hyperphagia with unintentional weight gain, guilt, a sense of worthlessness, and recurring thoughts of dying without suicidal ideations or intent. Since age 14, these had been present to varying degrees, without any complete resolution. For the past 9 years, he reported his symptom severity continually met criteria for a depressive episode with no periods of partial resolution.

Approximately 10 years prior to his presentation to the transcranial magnetic stimulation (TMS) clinic, the patient had deployed twice to Afghanistan with direct combat operational duties. Since that time, he admitted to feeling on edge, experiencing ease of startle, daytime intrusive recollections of combat, nightmares associated with the trauma, and efforts to avoid stimuli that reminded him of the trauma. He found relationships difficult due to a sense of disconnectedness and was profoundly socially isolated. There was also a sense of foreshortened future, which propagated a sense of hopelessness that his symptoms would not abate.

11.1.1 Developmental History

The patient denied any history of physical, emotional, or sexual abuse, with no history of legal troubles. He graduated high school on time and had earned a 4-year college degree. After serving in the military, he obtained work as a Department of Defense government employee. The patient had never been married and had no children. He had been without a sustained romantic relationship since returning from Afghanistan. His predominant recreational activity was weight training several hours each day.

11.1.2 Past Medical History

On presentation, there were no known medical illnesses and no history of seizures. He denied any metallic fragments or implants above the neckline. The patient had not received any surgical procedures to date. He took several supplements, including a daily multivitamin, Omega-3 supplements, probiotics, and amino acids. He did not report any allergies. He admitted to occasional 1–2 cigarette use when he was out with friends. There was no report of illicit drug use, including anabolic steroids.

Alcohol use was a concern. He admitted to daily use of alcohol, up to six drinks each night, over the past 10 years. He had developed a tolerance to alcohol, would have trouble limiting the amount he did drink, struggled to cut back his drinking, and admitted that it worsened his mood over time. Three months prior to presentation, he made a conscious effort to limit his intake on the advice of his therapist, drinking 3–4 drinks once a week, but he continued to struggle with strong alcohol cravings.

11.1.3 Family History

Both of his biological parents suffered from major depression. His sister was diagnosed with bipolar disorder type I and had been psychiatrically hospitalized once. There had been no suicides in the family.

11.1.4 Military History

The patient served a total of 7 years , achieving the rank of staff sergeant before an honorable discharge at the end of his enlistment period. During his deployment, he served with special operations units early in the Afghanistan campaign. He received several commendations for his service and never received any disciplinary actions.

11.1.5 Past Psychiatric History

No prior psychiatric hospitalizations were reported, and he had never attempted suicide. His psychiatric care was fragmented over the past 10 years. An attempt at exposure-based therapy several years prior was not tolerated. He was currently engaged in weekly cognitive behavioral therapy over the past 10 months. The patient had previously participated in several medication trials (Table 11.1).

Table 11.1

Drug, dose, and result of medication trials in which the patient participated

Trial date	Treatment (dose)	Result
2006	Lamictal starter pack	Rash
2006	Depakote (250 mg qday)	Tinnitus, sedation, dysarthria
2006–2008	Trazodone (100 mg qday)	Sedated during the day
2006–2009	Wellbutrin XL (300 mg qday)	Insomnia
2007–2013	Xanax (0.5 mg prn for anxiety)^a
2010–2013	Prozac (40 mg qday)	Weight gain and insomnia
2010–2013	Hydroxyzine (50 mg tid)	Ineffective

^a Used several times a week for anxiety

11.2 Diagnosis/Assessment

Psychiatric review of systems was otherwise unremarkable for symptoms of obsessive-compulsive disorder, generalized anxiety , panic disorder, simple phobia, mania , psychosis, eating disorder, or other psychiatric conditions not already mentioned.

11.2.1 Mental Status Examination

The patient arrived wearing a suit and tie, having come straight from his workplace. He was an articulate male, obviously muscular, and remained well composed and professional during the interview. His speech was slightly decreased in volume, but was of normal rate. His motor activity was normal. The patient described his mood as depressed, and while his affect was congruent, he did display brief periods of levity before drifting back to an apathetic baseline. Thought content was without suicidal or homicidal ideation. He denied delusions but did admit to recurrent thoughts of his own mortality. The patient’s thought process was goal directed, logical, and linear, with good insight, and intact judgment and impulse control. Cognition was intact as evidenced by a normal Montreal Cognitive Assessment (MoCA), ease of recall of his historical narrative, and varied vocabulary with appropriate low-frequency word use. The patient scored a 22 on the Patient Health Questionaire-9 (PHQ-9), which is indicative of severe depression. On the PTSD Checklist-Military version (PCL-M), the patient scored a 60, which is indicative of PTSD.

The patient’s blood was analyzed as follows: Complete blood count (CBC), comprehensive metabolic panel, B12, folate, lyme, thyroid stimulating hormone, rapid plasma reagin, HIV, total and free testosterone, which were all normal or negative. Total cholesterol was 230 mg/dl (125–200). Triglycerides were 194 mg/dl (< 150), high-density lipoprotein (HDL) was 38 mg/dl (> or = 40), and low-density lipoprotein (LDL) was 153 mg/dl (< 130).

Genetic analysis by commercial genetic assay (Genecept™ Assay) showed no clinically significant variations of Ankyrin G (ANK3), Methylenetetrahydrofolate reductase (MTHFR), Cytochrome P450 2D6 (CYP2D6), and Cytochrome P450 3A4 and 3A5 (CYP3A4/5). SLC6A4 was L(G)/L(G) variant suggesting the likelihood of poor or slow response and greater side effects with Selective serotonin reuptake inhibitors (SSRIs) [2]. Catechol methyl transferase (COMT) was Val/Val variant suggesting a reduction in frontal lobe dopamine [3] Serotonin 5HT2C receptor (5HT2C) was C/C variant which may be associated with an increased incidence of weight gain with atypical antipsychotics [4]. Dopamine receptor D2 (DRD2) was INS/DEL, which is associated with reduced efficacy and increased incidence of side effects with antipsychotics [5, 6]. calcium channel, voltage-dependent, L-type, alpha 1C subunit (CACNA1C) was A/A variant, which is a common variation associated with altered function of brain calcium channels [7], altered neuronal excitability, and possible mood instability. Cytochrome P450 2C19 (CYP2C19) was the Ultrarapid Metabolizer variant [8].

11.2.2 Assessment

This 35-year-old male has a genetic predisposition for mood disorders , likely accounting for much of his early age of onset and persistent symptoms despite the absence of a childhood trauma or maladaptive personality function. His genetic profile showing a variant of the serotonin transporter gene Solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4) suggests suboptimal response to SSRI’s. COMT Val/Val variant resulting in decreased frontal lobe dopamine may have contributed to his depressive symptomatology. His historically heavy use of alcohol likely hindered his recovery, and he remained at risk of full relapse if this was not addressed adequately. The patient’s admission of weight gain and hyperphagia associated with his depression were reflected with his hyperlipidemia, which also adds a risk of cardiovascular morbidity if not addressed.

Patients with preexisting psychiatric conditions remain at risk of development of PTSD, and many service members with direct combat exposure will endorse some degree of PTSD symptomatology [9]. The presence of PTSD raises the risk of comorbid depression and certainly will hinder recovery from the depressive episode.

The constellation of alcohol dependence, major depressive disorder, and PTSD form a self-perpetuating cycle, where each condition reinforces the others. Therefore, a treatment plan was developed to account for all three of these conditions to maximize the chance of full psychiatric recovery.

11.3 Treatment/Management

Patient preference should figure into any treatment plan, and for this case, the patient had indicated a wish to receive non-pharmacologic treatment for his psychiatric symptoms. The patient was also not interested in receiving electroconvulsive therapy due to stigma and fears of cognitive impairment.

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