CASE STUDY

BALANCING TREATMENT EFFICACY AND SIDE EFFECTS

David G. Daniel, MD

BACKGROUND
A 24-year-old man with no history of psychiatric treatment presented to the emergency room with paranoid delusions and poor self-care of 3 months duration. For the past 2 years the patient had been living alone in an apartment in San Francisco since having graduated from an Ivy League college. He had been unsuccessful in obtaining employment and eventually gave up trying after approximately 6 months. He became increasingly withdrawn and self-critical concerning his problems. There was no history of substance abuse or medical problems.

him and he found it uncomfortable that so many had thoughts of having sex with him. On mental status examination in the emergency room he was found to be cooperative; however, he became easily irritated with the examiners questions. His speech was fluent and normal in tempo. His mood was bright, as he was excited about all of the discoveries that he had made. His thought was goal directed, and he reported multiple grandiose, paranoid, and sexual delusions. He denied auditory or other hallucinations. He was cognitively fully intact. The patient did not want to be hospitalized, thus he was sent home on risperidone 2 mg to be taken at bedtime under the supervision of his family. He was to have psychiatric follow-up the next day. COURSE OF TREATMENT The patient was diagnosed with schizophrenia, paranoid type. Risperidone was increased to a dose of 4 mg over the course of a week with positive effect. He became less preoccupied about the FBI and was able to sleep approximately 5 hours per night. The risperidone was then increased to 5 mg per night and he experienced some increased sleep. He began to notice some loss of libido at this dose, which he attributed to someone poisoning him. He also began to experience galactorrhea, which was very disturbing, thus he refused to take his medications. It was explained to the patient that these symptoms could be secondary to the medications and he agreed to a trial of quetiapine. Quetiapine was titrated up to a dose of 200 mg in the morning and 400 mg at night. This agent was helpful in increasing sleep, and he was now able to sleep 7 hours per night. He no longer complained of sexual dysfunction or galactorrhea.

His family brought him to the emergency room after he began to become increasingly suspicious. The patient was fixated on the thought that members of the FBI were following him. He reported that he had discovered some of the most important scientific advances in a century and he thought that the government was trying to find out what they were. He was convinced that his apartment was bugged and asked the staff whether they might have government connections. However, he was calm and answered questions in a coherent fashion, although he refused to detail the nature of his discoveries. When asked why he wasnt more upset about the situation, he explained that he was too bright to be conned by some petty FBI agents into revealing his secrets. He admitted to hearing people talking about his brilliant discoveries as he walked down the street and wondered how they knew so much. He also reported that women were staring at

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However, he did experience daytime sedation. Attempts were made to switch more of the medication to bedtime, but he found it difficult to wake up in the morning. His appetite began to increase and he noted a weight gain of approximately 5 kg over the course of 1 month. He also still remained convinced of his major discoveries, although he found it easier to focus on his daily activities than previously. Attempts to increase quetiapine over 600 mg daily were not successful owing to daytime sedation. Because of the ongoing symptoms and inability to titrate the quetiapine to higher doses, it was decided to switch to olanzapine, which was titrated to a dose of 30 mg. His sleep improved on this regimen and he was able to take all of the medication at bedtime, reducing the daytime sedation. He gradually improved and, after approximately 3 months, he was much less delusional and more outgoing. He was able to handle a volunteer job for a few hours a week. However, he reported a marked increase in his appetite, with carbohydrate craving. Over the course of 3 months he gained an additional 10 kg. A fasting glucose was performed and the level was noted to be increased at 145 mg/dL; his baseline glucose had been 107 mg/dL before treatment. There was no previous history of hyperglycemia or family history of diabetes. Because of the multiple side effects that he had experienced, the patient decided that he wanted to stop medication. He did relatively well for a period of 3 months off of medication. He was able to maintain his volunteer position and continued to increase his social contacts. He began to make plans to return to school for graduate training. His appetite and weight decreased considerably. He eventually began to experience increased stress related to his life decisions. He became depressed and felt that his life was ruined. He began to ruminate and to feel guilty about all the years he had wasted. He felt that he would never again be able to make it in the real world. He was sleeping 3 to 4 hours per night and his appetite diminished markedly. His concentration was greatly diminished and he found that he even had difficulty concentrating on a television show. However, he was no longer delusional and did not report auditory or other hallucinations. Because the patient now presented with a nondelusional major depression, further history was obtained to determine whether the patient met criteria for schizoaffective disorder, depressed or bipolar disorder,

depressed phase. The family reported that as a child the patient was a socially engaging individual with many friends. He had some difficulties with his behavior at times and tended to have severe temper tantrums when not getting his way during his grade school years. At times he would be moody and sulk for days at a time. He had difficulty sitting still and concentrating. Although his teachers had talked to the parents about the possibility of attention deficit disorder, the parents were not interested in medications or further evaluation of the child. In junior high school his behavior improved considerably and he did well academically and socially through college. During the period from age 22 to 24 years when he became increasingly withdrawn after college, he was thought by his parents to be very depressed. He complained of feeling sad, but he attributed this entirely to his life circumstances. His parents did not report having any psychiatric problems themselves; however, the paternal grandfather was described as a very moody, irritable, and angry individual. The patients sister was similarly described as an angry and irritable individual. She has refused psychiatric treatment, as she thinks that she only becomes angry in reaction to other peoples negative attitudes. At this point in the treatment, the diagnosis was changed to bipolar disorder and it was decided to initiate a trial of lamotrigine. A dose of 25 mg was initiated and slowly titrated to minimize the risk of a rash. As the dose was raised to 50 mg, the patient started to become somewhat suspicious and he thought that people were talking about him behind his back. Aripiprazole was initiated and the dose was increased to 30 mg. Lamotrigine was titrated slowly to 200 mg over several months. No evidence of rash was noted over the titration period. Zolpidem 10 mg was used for insomnia as needed. The patient improved considerably on this regimen. His mood became brighter and he was more optimistic. After 6 months he continued to be free of psychotic symptoms and appeared to be near his premorbid level of function. DISCUSSION This case illustrates the many difficulties encountered by the clinician in diagnosing and treating patients with fluctuating psychotic and affective symptoms. The grandiose, sexual, and paranoid delusions noted on the initial presentation may be present in patients with paranoid schizophrenia or bipolar disor-

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der. Although the initial diagnosis of paranoid schizophrenia was a reasonable one in this individual, this diagnosis was probably made in the absence of a detailed clinical history. The 2-year period of social withdrawal before the acute psychotic episodes could have been a prodromal state before a full schizophrenic presentation. However, on further questioning of the parents, there appeared to be a very significant depressive element during this period. There are several other clues that a bipolar disorder is the more appropriate diagnosis. Early childhood history indicates a socially outgoing and engaging individual with difficulties with attention and hyperactivity. Although the school entertained a diagnosis of attention deficit disorder, the presence of severe temper tantrums and moodiness should alert the clinician to the possibility of an early onset bipolar disorder. The family history of anger and irritability in the paternal grandfather and the sister is also suggestive of a family history of bipolar disorder, although a full manic depressive syndrome is not delineated in either of these individuals. The patient had a partial response to risperidone and quetiapine and a more robust response to olanzapine. The apparent better response to olanzapine may have been a function of length of time of total treatment, as it often takes several months before maximum symptom relief is obtained. The case points out the difficulty and the importance of balancing effective treatment response while minimizing the side-effect burden.

Weight gain is most frequently associated with olanzapine and clozapine, although risperidone and quetiapine may also induce weight increases. However, aripiprazole and ziprasidone tend to be weight neutral. Sexual side effects with risperidone are not uncommon and may be associated with prolactin increases. Galactorrhea occurs in a smaller number of patients on risperidone and can be very disturbing to males and females. The sedation observed with quetiapine is commonly seen with this agent and limited the clinical use of this agent. Hyperglycemia is also frequently encountered with antipsychotic treatment and is most problematic for olanzapine- and clozapine-treated patients. Caution should be observed with this side effect as diabetic ketoacidosis and even deaths have been reported with atypical antipsychotic therapy. Hyperglycemia may be partly related to weight gain, as blood glucose tends to increase with increasing body weight. However, direct medication-induced insulin resistance may also raise blood sugar, even in the absence of weight gain. The patient had a marked positive response to lamotrigine and aripiprazole during the acute depressive episode. Lamotrigine must be titrated slowly because there is a risk of a serious rash with rapid titration. Ziprasidone may have been used in lieu of aripiprazole, as there is also a low potential for weight gain and sexual dysfunction with this agent.

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