Maria C Catalano’s research while affiliated with James A. Haley Veterans Hospital and other places

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.

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.

Ramelteon is a melatonin receptor agonist that is approved for the treatment of insomnia. It is widely used due to its relatively benign side effect profile and lack of dependence or withdrawal. Due to its tolerability, clinicians have attempted to utilize ramelteon to normalize the sleep/wake patterns in patients with delirium as a safer alternative to antipsychotics or other medications. We present the case of a 75-year-old man with long-standing dementia who was hospitalized due to mental status changes, agitation, and sleep disturbance. After addressing possible underlying causes with minimal improvement, the team initiated treatment with ramelteon (8mg nightly) which resulted in rapid improvement of symptoms. Uses and mechanisms of action of ramelteon will be reviewed, as well as current pharmacologic treatments of delirium. Prior research studies and case reports regarding the use of ramelteon in the treatment of delirium will be discussed and suggestions made regarding possible areas of future study.

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. Method: 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 compares 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 associoation between the use of topiramate and the developmenrt of hallucinations. Even though the average daily topiramate dose associated with the development of hallucinations in previously reported cases was 150 mg in women and 181.25 mg in men, hallucinations can occur at lower doses (as low as 50 mg daily) as well.

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.

Vampiristic behaviors are rarely seen clinically and less than 100 cases have been reported in the world literature to date. A distinction is usually made as to whether the patient drinks their own blood or the blood of others. We describe a 38-year-old patient who had vampiristic thoughts and fantasies that began in adolescence, but did not act on these thoughts until after she suffered a traumatic brain injury with a three-week loss of consciousness while serving in the military. Brain imaging showed focal damage to her bilateral frontal lobes. Psychological testing demonstrated impairment of executive function. We review the proposed diagnostic criteria for vampirism and discuss how behavioral disinhibition may have affected the emergence into behavior of her previously inhibited vampiristic thoughts.

Takotsubo cardiomyopathy is an acute coronary syndrome that is believed to be brought on by stress. Symptoms, which are similar to an acute myocardial infarction, include chest pain, shortness of breath, arrhythmias, and cardiogenic shock, and the electrocardiogram often shows ST and T wave changes. Left ventricular wall hypokinesis along with a significantly reduced ejection fraction are seen on echocardiogram. The great majority of these symptoms all occur in the absence of occlusive disease. Many cases have been reported in which the development of takotsubo cardiomyopathy was associated with serotonin norepinephrine reuptake inhibitors and tricyclic antidepressants. However, no cases of takotsubo cardiomyopathy have been reported involving selective serotonin reuptake inhibitors. This article presents the case of a 51-year-old woman receiving stable therapy with fluoxetine who developed takotsubo cardiomyopathy after an acute stress. We also discuss the clinical presentation of takotsubo cardiomyopathy, review possible causes, and discuss the treatment of depressive symptoms in patients who are at increased risk of developing this illness.

Lamotrigine is an anticonvulsant medication that also has utility in the treatment of bipolar disorder. It has been associated with many side effects, including rashes that can progress to Stevens-Johnson syndrome or toxic epidermal necrolysis. It has also been associated with the development of motor tics, most commonly in the head, neck, and shoulders. We will now present the case of a 45-year-old woman who developed tics that involved the entire left side of her body after her dose of lamotrigine was increased from 200mg daily (2.0mg/kg/day) to 225 mg daily (2.3mg/kg/day). We will review the prior cases of lamotrigine induced tics, and compare them to the circumstances surrounding our patient. We will also discuss the neurobiology of tics and make suggestions to improve the tics, based on the reported cases.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder characterized by IgG autoantibodies directed against the NR1 subunit of the NMDA glutamate receptor. Psychiatric symptoms are common and include psychosis, mania, depressed mood, aggression, and speech abnormalities. Neurological symptoms such as seizures, decreased responsiveness, dyskinesias, and other movement abnormalities and/or autonomic instability are frequently seen as well. We present the case of a woman who was followed up at our facility for over 14 years for the treatment of multiple neuropsychiatric symptoms. Initially, she presented with paresthesias, memory loss, and manic symptoms. Nine years later, she presented to our facility again, this time with left sided numbness, left eyelid droop, and word finding difficulties. Finally, five years later, she presented with manic symptoms, hallucinations, and memory impairment. During her hospitalization, she subsequently developed catatonic symptoms and seizures. During her stay, it was discovered that she was positive for anti-NMDA receptor antibodies and her symptoms responded well to appropriate therapy. This case demonstrates that it may be useful for clinicians to consider screening for anti-NMDA receptor antibodies in long-term patients with neuropsychiatric symptoms that have not adequately responded to therapy.