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His family brought him to the emergency roomafter he began to become increasingly suspicious. Thepatient was fixated on the thought that members ofthe FBI were following him. He reported that he haddiscovered some of the most important scientificadvances in a century and he thought that the govern-ment was trying to find out what they were. He wasconvinced that his apartment was bugged and askedthe staff whether they might have government con-

nections. However, he was calm and answered ques-tions in a coherent fashion, although he refused todetail the nature of his discoveries. When asked whyhe wasnt more upset about the situation, he explainedthat he was too bright to be conned by some petty FBIagents into revealing his secrets. He admitted to hear-ing people talking about his brilliant discoveries as hewalked down the street and wondered how they knewso much. He also reported that women were staring at

him and he found it uncomfortable that so many hadthoughts of having sex with him.

On mental status examination in the emergencyroom he was found to be cooperative; however, hebecame easily irritated with the examiners questions.His speech was fluent and normal in tempo. His moodwas bright, as he was excited about all of the discover-ies that he had made. His thought was goal directed,and he reported multiple grandiose, paranoid, and sex-ual delusions. He denied auditory or other hallucina-tions. He was cognitively fully intact.

The patient did not want to be hospitalized, thushe was sent home on risperidone 2 mg to be taken atbedtime 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 of4 mg over the course of a week with positive effect. Hebecame less preoccupied about the FBI and was able tosleep approximately 5 hours per night. The risperidonewas then increased to 5 mg per night and he experi-enced some increased sleep. He began to notice someloss of libido at this dose, which he attributed to some-one poisoning him. He also began to experience galac-

torrhea, which was very disturbing, thus he refused totake his medications.

It was explained to the patient that these symptomscould be secondary to the medications and he agreedto a trial of quetiapine. Quetiapine was titrated up toa dose of 200 mg in the morning and 400 mg at night.This agent was helpful in increasing sleep, and he wasnow able to sleep 7 hours per night. He no longercomplained of sexual dysfunction or galactorrhea.

CASE STUDY

BALANCING TREATMENT EFFICACY AND SIDE EFFECTS

David G. Daniel, MD

BACKGROUND

A 24-year-old man with no history of psychiatrictreatment presented to the emergency room withparanoid delusions and poor self-care of 3 monthsduration. For the past 2 years the patient had beenliving alone in an apartment in San Francisco sincehaving graduated from an Ivy League college. Hehad been unsuccessful in obtaining employment andeventually gave up trying after approximately 6months. He became increasingly withdrawn andself-critical concerning his problems. There was nohistory of substance abuse or medical problems.

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However, he did experience daytime sedation.Attempts were made to switch more of the medicationto bedtime, but he found it difficult to wake up in themorning. His appetite began to increase and he noted

a weight gain of approximately 5 kg over the course of1 month. He also still remained convinced of hismajor discoveries, although he found it easier to focuson his daily activities than previously. Attempts toincrease quetiapine over 600 mg daily were not suc-cessful owing to daytime sedation.

Because of the ongoing symptoms and inability totitrate the quetiapine to higher doses, it was decided toswitch to olanzapine, which was titrated to a dose of30 mg. His sleep improved on this regimen and he wasable to take all of the medication at bedtime, reducingthe daytime sedation. He gradually improved and,

after approximately 3 months, he was much less delu-sional and more outgoing. He was able to handle a vol-unteer job for a few hours a week. However, hereported a marked increase in his appetite, with carbo-hydrate craving. Over the course of 3 months hegained an additional 10 kg. A fasting glucose was per-formed and the level was noted to be increased at 145mg/dL; his baseline glucose had been 107 mg/dLbefore treatment. There was no previous history ofhyperglycemia or family history of diabetes.

Because of the multiple side effects that he hadexperienced, the patient decided that he wanted to

stop medication. He did relatively well for a period of3 months off of medication. He was able to maintainhis volunteer position and continued to increase hissocial contacts. He began to make plans to return toschool for graduate training. His appetite and weightdecreased considerably.

He eventually began to experience increased stressrelated to his life decisions. He became depressed andfelt that his life was ruined. He began to ruminate andto feel guilty about all the years he had wasted. He feltthat he would never again be able to make it in thereal world. He was sleeping 3 to 4 hours per night

and his appetite diminished markedly. His concentra-tion was greatly diminished and he found that he evenhad difficulty concentrating on a television show.However, he was no longer delusional and did notreport auditory or other hallucinations.

Because the patient now presented with a nondelu-sional major depression, further history was obtainedto determine whether the patient met criteria forschizoaffective disorder, depressed or bipolar disorder,

depressed phase. The family reported that as a childthe patient was a socially engaging individual withmany friends. He had some difficulties with his behav-ior at times and tended to have severe temper tantrums

when not getting his way during his grade schoolyears. At times he would be moody and sulk for daysat a time. He had difficulty sitting still and concen-trating. Although his teachers had talked to the parentsabout the possibility of attention deficit disorder, theparents were not interested in medications or furtherevaluation of the child. In junior high school hisbehavior improved considerably and he did well aca-demically and socially through college. During theperiod from age 22 to 24 years when he becameincreasingly withdrawn after college, he was thoughtby his parents to be very depressed. He complained of

feeling sad, but he attributed this entirely to his life cir-cumstances. His parents did not report having anypsychiatric problems themselves; however, the paternalgrandfather was described as a very moody, irritable,and angry individual. The patients sister was similarlydescribed as an angry and irritable individual. She hasrefused psychiatric treatment, as she thinks that sheonly becomes angry in reaction to other peoples neg-ative attitudes.

At this point in the treatment, the diagnosis waschanged to bipolar disorder and it was decided to ini-tiate a trial of lamotrigine. A dose of 25 mg was initi-

ated and slowly titrated to minimize the risk of a rash.As the dose was raised to 50 mg, the patient started tobecome somewhat suspicious and he thought that peo-ple were talking about him behind his back.Aripiprazole was initiated and the dose was increasedto 30 mg. Lamotrigine was titrated slowly to 200 mgover several months. No evidence of rash was notedover the titration period. Zolpidem 10 mg was usedfor insomnia as needed. The patient improved consid-erably on this regimen. His mood became brighter andhe was more optimistic. After 6 months he continuedto be free of psychotic symptoms and appeared to be

near his premorbid level of function.

DISCUSSION

This case illustrates the many difficulties encoun-tered by the clinician in diagnosing and treatingpatients with fluctuating psychotic and affective symp-toms. The grandiose, sexual, and paranoid delusionsnoted on the initial presentation may be present inpatients with paranoid schizophrenia or bipolar disor-

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der. Although the initial diagnosis of paranoid schizo-phrenia was a reasonable one in this individual, thisdiagnosis was probably made in the absence of adetailed clinical history. The 2-year period of social

withdrawal before the acute psychotic episodes couldhave been a prodromal state before a full schizophrenicpresentation. However, on further questioning of theparents, there appeared to be a very significant depres-sive element during this period. There are several otherclues that a bipolar disorder is the more appropriatediagnosis. Early childhood history indicates a sociallyoutgoing and engaging individual with difficultieswith attention and hyperactivity. Although the schoolentertained a diagnosis of attention deficit disorder,the presence of severe temper tantrums and moodinessshould alert the clinician to the possibility of an early

onset bipolar disorder. The family history of anger andirritability in the paternal grandfather and the sister isalso suggestive of a family history of bipolar disorder,although a full manic depressive syndrome is notdelineated in either of these individuals.

The patient had a partial response to risperidone andquetiapine and a more robust response to olanzapine.The apparent better response to olanzapine may havebeen a function of length of time of total treatment, as itoften takes several months before maximum symptomrelief is obtained. The case points out the difficulty andthe importance of balancing effective treatment response

while minimizing the side-effect burden.

Weight gain is most frequently associated witholanzapine and clozapine, although risperidone andquetiapine may also induce weight increases. However,aripiprazole and ziprasidone tend to be weight neutral.

Sexual side effects with risperidone are not uncommonand may be associated with prolactin increases.Galactorrhea occurs in a smaller number of patients onrisperidone and can be very disturbing to males andfemales. The sedation observed with quetiapine iscommonly seen with this agent and limited the clini-cal use of this agent. Hyperglycemia is also frequentlyencountered with antipsychotic treatment and is mostproblematic for olanzapine- and clozapine-treatedpatients. Caution should be observed with this sideeffect as diabetic ketoacidosis and even deaths havebeen reported with atypical antipsychotic therapy.

Hyperglycemia may be partly related to weight gain, asblood glucose tends to increase with increasing bodyweight. However, direct medication-induced insulinresistance may also raise blood sugar, even in theabsence of weight gain.

The patient had a marked positive response to lam-otrigine and aripiprazole during the acute depressiveepisode. Lamotrigine must be titrated slowly becausethere is a risk of a serious rash with rapid titration.Ziprasidone may have been used in lieu of aripipra-zole, as there is also a low potential for weight gain andsexual dysfunction with this agent.

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NOTES