Antidepressant Augmentation: A Review of the Literature and a Review of the Pharmacoeconomic Considerations.

PURPOSE: Antidepressant augmentation strategies for treatment-resistant depression (TRD) are discussed here with an analysis of patient out-of-pocket costs for various medications. The choice of agent ranges from newer atypical antipsychotics (aripiprazole, brexpiprazole, quetiapine) to older agents including buspirone, liothyronine (T3), and lithium. We sought to better understand the differences among these agents to aid in clinical decision making. METHODS: We conducted a focused review of the support for each of the aforementioned agents in antidepressant augmentation. We then compared the approximate out-of-pocket cost for each medication during a typical augmentation trial using the typical prescription costs on ClinCalc.com derived from the Medical Expenditure Panel Survey. We calculated the cost to achieve response for one patient with TRD based on the number needed to treat (NNT). FINDINGS: We observed significant variance in cost to achieve response based on the NNT derived from our review of each of the medications. For example, the overall out-of-pocket cost for one patient to achieve response with aripiprazole (the costliest generic agent) could cover lithium prescriptions for 4 to 5 patients with TRD to achieve response. Although brexpiprazole was estimated separately because of its brand name cost, we estimated that 324 patients receiving lithium could achieve response for same cost of single patient receiving brexpiprazole. IMPLICATIONS: These findings suggest that among augmentation agents, there are differences in cost that may be highly important in clinical decision making. Other issues of medication monitoring may incur additional costs, and brand name medications offer significantly greater complexity and potential out-of-pocket costs to patients. The use of lithium as a first-line agent for TRD should be considered based on low cost, lowest NNT, and data in support of its efficacy.

Clinical repetitive transcranial magnetic stimulation for veterans with major depressive disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is a relatively new treatment modality for patients with major depressive disorder (MDD). Numerous studies have demonstrated the efficacy of TMS for MDD in the general population. However, there is limited information regarding clinical outcomes among veterans receiving TMS for MDD. METHODS: The clinical outcome and characteristics of all veterans with MDD who were treated with TMS as outpatients at the James A. Haley Veterans' Hospital from October 2013 to December 2016 were assessed. RESULTS: Among 40 patients who received TMS, there was a significant improvement of depressive symptoms using the Quick Inventory of Depressive Symptomatology-Self-Report (45% response, 20% remission) and the Montgomery-Åsberg Depression Rating Scale (61.9% response, 42.9% remission). In addition to significant improvement in depressive symptoms, self-report of anxiety symptoms and function significantly improved. TMS was generally well tolerated, with only a small percentage of patients discontinuing treatment due to side effects. No seizures or persistent adverse effects were observed or reported. CONCLUSIONS: TMS is an effective and well-tolerated option for MDD in a veteran population with significant treatment resistance and multiple comorbidities.

Delirium Secondary to Lamotrigine Toxicity.

BACKGROUND: Lamotrigine is a phenyltriazine medication that has been approved by the United States Food and Drug Administration as monotherapy and as an adjunctive agent for the treatment of seizure disorder. It was later approved by the FDA for the treatment of bipolar disorder. Lamotrigine is generally well tolerated by patients, but some serious symptoms can occur during treatment. These severe side effects include rashes and multi-organ failure. Lamotrigine has also been associated with the development of mental status changes, frequently when used concurrently with other medications that may impact the metabolism of lamotrigine. OBJECTIVE: To present the case of a 65-year-old man being treated with lamotrigine and valproic acid who developed mental status changes after the addition of sertraline to his medication regimen, and to compare this case to existing cases reported in the literature. DISCUSSION: Our case adds to the existing literature by demonstrating that patients may experience adverse medication effects despite lamotrigine levels that are normally considered to be in the therapeutic range, highlighting the importance of clinical correlation when obtaining medication levels. CONCLUSION: Clinicians should use caution interpreting lamotrigine levels when working up delirium, as normal levels may not rule out the development of lamotrigine toxicity.

Impact of Comorbid PTSD on Outcome of Repetitive Transcranial Magnetic Stimulation (TMS) for Veterans With Depression.

OBJECTIVE: A recent randomized controlled trial of repetitive transcranial magnetic stimulation (TMS) for major depressive disorder (MDD) in veterans raised the question of whether comorbid posttraumatic stress disorder (PTSD) negatively impacted the outcome of TMS in veterans. To address this, a quality database was analyzed to compare outcomes of MDD treated with TMS in veterans with and without comorbid PTSD. METHODS: The clinical outcomes of all consecutive veterans with MDD treated with TMS at the James A. Haley Veterans' Hospital as outpatients from October 2013 through September 2018 were included. Patients were initially evaluated by an experienced psychiatrist, and the diagnosis of MDD was made by clinical evaluation per DSM-IV-TR/DSM-5 criteria. At the start of treatment, after every 5 treatments, and at the end of treatment, patients were assessed with self-report and clinician-rated scales of depression. All data were abstracted from an existing quality database. RESULTS: Among the 118 patients treated with TMS for depression, 55 (47%) had comorbid PTSD and 63 (53%) had no comorbid PTSD. Response and remission rates by score on the Montgomery-Asberg Depression Rating Scale were similar between patients with PTSD (52.5% and 40.9%, respectively) and without PTSD (53.8% and 35.6%, respectively). No seizures or persistent adverse effects were observed or reported in either group. CONCLUSIONS: Comorbid PTSD did not impact the outcome of TMS for depression in this sample of veterans. Future studies should include formal ratings of PTSD to determine if the severity of PTSD affects the outcome.

Nortriptyline Abuse: A Case Report and Review of the Literature.

The tricyclic antidepressants have long been a tool in the physician's armament for numerous indications, the most prominent of which being depression. Although their efficacy and side effects have been well documented, less known is their abuse. Prior literature has discussed this more for the tertiary amines such as amitriptyline, but currently, there are no documented cases of abuse with the secondary amine nortriptyline. This article reviews the prior literature in regard to tricyclic antidepressants and anticholinergics as substances of abuse, the proposed mechanisms of this, and susceptible populations, as well as a case review of a patient who admitted to using nortriptyline for its "buzz."

Leukopenia Associated with Risperidone Treatment.

Risperidone is an atypical antipsychotic agent that was originally approved by the United States Food and Drug Adminstration for the treatment of schizophrenia. There are many side effects that are frequently associated with the use of risperidone. These include weight gain, anxiety, extra-pyramidal side effects, and elevated prolactin levels. More infrequently, the use of risperidone has been linked to leukopenia. We will now present the case of a 66-year-old gentleman who developed leukopenia after the initiation of risperidone to control agitation due to delirium. We will review the previous cases of leukopenia associated with risperidone, and will review possible risk factors for the development of leukopenia, based on the reported cases.

Hallucinations Associated with Topiramate Therapy: A Case Report and Review of the Literature.

BACKGROUND: Topiramate is a medication that is approved as both monotherapy and adjunctive treatment of seizure disorder in adults and adolescents. It is also approved for migraine prophylaxis. It has been associated with many side effects, including weight loss and the development of renal stones. It has also been associated with various central nervous system side effects such as dizziness, nervousness, parasthesias, and fatigue. Less commonly, it has been associated with the development of psychotic symptoms such as hallucinations. OBJECTIVE: To describe the relationship between the administration of topiramate and the development of hallucinations in this patient. METHODS: We will now present the case of a 32-year-old man who developed auditory hallucinations after initiating a relatively low dose of topiramate (25mg twice daily) for the treatment of chronic pain. We will review the prior cases of topiramate induced hallucinations, and discuss how these cases compare to the case we have described. We will review the treatment of these hallucinations. RESULTS: In this case, there was a close temporal relationship between the initiation of topiramate and the onset of auditory hallucinations. CONCLUSION: This case supports the previous reports describing the association between the use of topiramate and the developmenrt of hallucinations. Although the average daily topiramate dose associated with the development of hallucinations in previously reported cases was 150 mg in women and 181 mg in men, hallucinations can occur at lower doses (as low as 50 mg daily) as well.