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.

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.

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.

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.

Vampiristic behaviors in a patient with traumatic brain injury induced disinhibition.

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.

The Use of Fluoxetine in a Patient With Takotsubo Cardiomyopathy.

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 Induced Whole Body Tics: A Case Report and Literature Review.

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 200 mg daily (2.0 mg/kg/day) to 225 mg daily (2.3 mg/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-NMDA Receptor Encephalitis in a Patient with Previous Psychosis and Neurological Abnormalities: A Diagnostic Challenge.

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.

Dystonia associated with lamotrigine therapy: a case report and review of the literature.

The association of extrapyramidal side effects (EPS) with the use of conventional antipsychotics is well established, however, EPS can occur during treatment with anticonvulsant medications as well. We will present the case of a patient who developed an acute dystonic reaction during treatment with lamotrigine and again during re-challenge with the same agent. We will review common side effects of this medication and the previous reports of lamotrigine-associated dystonias. We will also discuss a possible underlying mechanism.

Covert dyskinesia associated with aripiprazole: a case report and review of the literature.

The atypical antipsychotic agents are felt by many to have a lower risk of inducing the development of dyskinetic movements than the conventional antipsychotic agents agents such as haloperidol and fluphenazine. However, that does not mean that treatment with the atypical antipsychotic agents carries no risk of developing dyskinesias. To the contrary, all of the atypical antipsychotic agents, including aripiprazole, have been associated with the induction of dyskinetic movements. We will present the case of a patient who developed a covert dyskinesia that manifested shortly after the discontinuation of aripiprazole. We will review the use of aripiprazole and the adverse effects most commonly associated with its use. We will also discuss the risk factors associated with the development of tardive dyskinesia and review the different clinical variations (withdrawal dyskinesia, covert dyskinesia, tardive diskinesia) of medication-induced dyskinesias.

Memantine and catatonia: a case report and literature review.

Catatonia is a movement disorder with various possible etiologies. The majority of cases are associated with an underlying mood or psychotic disorder, while others are caused by medical conditions. Currently, benzodiazepines are the first-line psychopharmacologic agents in the treatment of catatonia. However, several cases have been reported in which treatment with memantine proved to be effective. We present the case of a 92-year-old female with major depressive disorder and associated catatonic symptoms. In this case, the patient's symptoms remitted quickly after the initiation of memantine. We review the possible causes of catatonia and pharmacologic treatments for the condition and highlight the possible benefits of N-methylD-aspartic acid receptor antagonists such as memantine in the treatment of catatonia.

Charles Bonnet syndrome: are medications necessary?

Charles Bonnet syndrome (CBS) is a clinical entity in which patients develop vivid visual hallucinations in the absence of psychiatric illness. In the great majority of cases, a decline in visual acuity precedes the development of CBS. The patient maintains intact reality testing and recognizes that the hallucinations are not real. There is no definitive cure for CBS, although various pharmacologic agents, behavioral strategies, and ophthalmologic interventions have been used in an attempt to reduce or relieve symptoms. We present the case of a 79-year-old man who presented with the onset of vivid visual hallucinations after developing cataracts. We also review previous case reports of CBS and discuss treatment options.

Lactic acidosis, hypotension, and sensorineural hearing loss following intentional metformin overdose.

Metformin and glyburide are antihyperglycemic agents that are widely used in the United States. There have been several cases of overdose of these medications reported in the world literature. Glyburide overdose is associated with hypoglycemia that can be severe, while metformin overdoses have been associated with lactic acidosis. In many cases of metformin overdose, lactic acidosis has led to profound hypotension and respiratory failure. In this article we will present the case of a 49-year-old man who ingested 52 grams of metformin and 350 mg of glyburide in a suicide attempt. The patient developed hypoglycemia, lactic acidosis, hypotension, respiratory failure and a profound sudden sensorineural hearing loss. We discuss prior cases of overdose with these agents, and the connection between overdose and the development of sudden sensorineural hearing loss.

Olanzapine for the treatment of acquired neurogenic stuttering.

Stuttering is a vocal phenomenon, which manifests itself as disturbances in speech fluency. While stuttering is most commonly treated with speech therapy and psychotherapy, a number of antipsychotic agents have been investigated as possible treatments. We present the case of a 37-year-old man who developed a post-concussive syndrome with psychosis and associated stuttering after his second exposure to a blast from an improvised explosive device (IED). After treatment with olanzapine, both his psychosis and his stuttering showed significant improvement. We also discuss stuttering and review previous studies that have investigated antipsychotic use in stuttering.

Serotonin syndrome associated with the use of escitalopram.

Escitalopram is the newest selective serotonin reuptake inhibitor (SSRI) available for use in the United States. It has been approved for the treatment of major depression and generalized anxiety disorder. It is the S-enantiomer of the SSRI citalopram and is highly serotonin specific as it has minimal effect on the reuptake of dopamine or norepinephrine. It is also a well-tolerated medication, with a side-effect profile comparable to the other SSRIs. While a number of side effects have been seen during escitalopram therapy, such as insomnia, nausea, and increased sweating, there are no reported cases of serotonin syndrome associated with escitalopram therapy to date. We present the case of a 24-year-old woman who developed serotonin syndrome after an increase in her escitalopram to 30 mg/day. We will review the diagnostic criteria of serotonin syndrome and the clinical scenarios in which serotonin syndrome can develop. We will also discuss the proposed treatments and role that polypharmacology may play in the development of this clinical entity.

A survey of psychiatry residency programs: association between program characteristics and success in the 2003 NRMP.

While the number of medical students entering psychiatry has increased since the 1990's, little has been written about the program characteristics that draw students to specific psychiatry residency programs. We developed a survey regarding residency program characteristics and distributed it to the chief residents of each psychiatry residency program in the USA. Survey results were tabulated, and the presence of specific characteristics were correlated to the 2003 National Resident Matching Program (NRMP) results. We found that the presence of a substance abuse, geriatric psychiatry or a child and adolescent psychiatry fellowship were all associated with increased NRMP success. Programs with regular resident meetings had significantly higher success in the NRMP than those programs without meetings. Programs that had six or more PGY-I positions available in the NRMP revealed a trend towards higher NRMP success than smaller programs. Finally, in some cases, higher intern salaries were associated with higher NRMP success.