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A large and growing body of research demonstrates the superiority of the newer atypical antipsychotics over the earlier antipsychotic medications, usually termed first-generation or conventional agents. The newer medications have been shown to be superior in terms of their effects on positive symptoms, negative symptoms, cognition, quality of life, and compliance while reducing the number of hospitalizations, visits to the emergency department, and side effects such as extrapyramidal symptoms and elevated prolactin concentrations (1,2). As a result, atypical antipsychotics are frequently recommended as the first treatment choice.
Although most patients prefer atypical antipsychotics, some patients adamantly resist switching from conventional antipsychotics, even when side effects or a less-than-optimal response suggest that switching might be beneficial. To our knowledge, nothing has been written about this phenomenon. In this column we describe five such cases.
Mr. A is a 55-year-old Filipino man who experienced his first psychotic break at the age of 36. At that time, he was hearing voices and believed that people were talking about him and trying to harm him. He also reported feeling depressed. A diagnosis of paranoid schizophrenia was made, and the patient started treatment with thiothixene, the dosage of which was gradually reduced as he improved.
For two years, Mr. A was stable. He then stopped taking his medication for about six months, and his psychosis worsened. He became more paranoid and delusional and had to be hospitalized. Treatment with thiothixene was restarted, and Mr. A reported improvement. However, he also complained of extrapyramidal symptoms, for which his treating physician prescribed benztropine. One year later, Mr. A complained of abnormal involuntary movements of his mouth and tongue and of muscular stiffness. A few months later he reported feeling shaking in his hands. His thiothixene dosage was reduced, and his motor symptoms improved.
Two years later, Mr. A complained of restlessness and continuous tapping of his right foot. He said he could not sit still. The thiothixene dosage was again reduced and the benztropine dosage increased. He reported improvement in his akathisia over the next year. Later in the course of his illness, Mr. A reported nervousness and difficulties in sleeping, along with an almost constant feeling of sadness. These symptoms were well controlled by adding lithium to his medication regimen and by increasing his thiothixene dosage.
Mr. A has continued to take thiothixene for the past seven years, and he has had no psychiatric hospitalizations during this time. His psychotic symptoms have been well controlled. He reports that auditory hallucinations have been infrequent and do not bother him much, and his paranoid feelings are less intense. Mr. A's treating psychiatrists have made several attempts to switch his medication from thiothixene to an atypical antipsychotic and have repeatedly explained to him the differences in effectiveness and side effects. However, Mr. A has continued to express his complete satisfaction with his current medication.
Mr. B is a 58-year-old African-American man who was first admitted to our clinic in 1993 complaining of a long history of auditory hallucinations, paranoid delusions, and a perpetual feeling of sadness. He was not able to recall his first psychotic episode, but he had had multiple hospitalizations and had taken many different medications. When Mr. B was first seen in our clinic, a diagnosis of schizoaffective disorder was made.
Mr. B started treatment with haloperidol and benztropine. He reported improvement, but his mood remained sad, which prompted the addition of sertraline. One year later the auditory hallucinations worsened, and Mr. B reported hearing voices all the time. His haloperidol dosage was gradually increased. Over the next year, Mr. B became stable and reported fewer auditory hallucinations and less paranoia, but he began to complain of perioral and tongue movements and, a few months later, of muscular stiffness, restlessness, and hand tremor. The haloperidol dosage was decreased and the benztropine dosage increased, and he reported improvement in his abnormal involuntary movements.
Mr. B was told about the new atypical antipsychotics and was advised to switch to one of them, but he refused. He said that he has felt stable since he started taking the haloperidol and has not needed to be admitted to the hospital over the past seven years. He is not willing to switch to any other medication even though he knows about potential severe side effects, including tardive dyskinesia.
Mr. C is a 48-year-old Hispanic man who first came to our clinic after being referred by our emergency department because of suicidal ideation, auditory hallucinations, paranoid delusions, and bizarre thinking. A diagnosis of paranoid schizophrenia was made, and treatment with thiothixene and benztropine was started.
Mr. C started experiencing restlessness and persistent tapping of his right foot. Diphenhydramine was added to his regimen, and his thiothixene dosage was gradually reduced. Although his akathisia improved, his psychosis worsened. He became more delusional and paranoid, and he was admitted to the hospital because of hostility and aggressive behavior. Mr. C's thiothixene dosage was gradually increased. His psychosis was stabilized, and he was again discharged to our clinic while taking thiothixene and benztropine.
Mr. C then began a trial of 4 mg of risperidone a day in a research study. However, after two weeks he reported dissatisfaction with how he felt while taking risperidone and demanded that his previous medication regimen be restored immediately, which members of his family supported. Mr. C said that he was totally satisfied with thiothixene and that he did not like the risperidone. Although he understands the risk of developing tardive dyskinesia, akathisia, and other side effects while taking thiothixene, he feels stable. The fact that he has not had be admitted to the hospital during the past five years makes him think that thiothixene is the best choice for him.
Mr. D is a 50-year-old Hispanic man with a long history of schizophrenia, first diagnosed when he was 25. He has been followed up in our clinic since 1988. Mr. D complained of having occasional auditory hallucinations of voices making derogatory comments and of experiencing periods of paranoid delusions. He denied having visual hallucinations and suicidal or homicidal ideation.
Mr. D initially was treated with thiothixene and a year later was switched to haloperidol. He has been generally stable while taking haloperidol, experiencing no side effects other than slight shoulder stiffness and mild finger tremors, for which benztropine was prescribed. However, he continues to describe chronic auditory hallucinations and delusions.
Mr. D has been consistently reluctant to try any new medication. At one point his haloperidol dosage was increased, but he was unable to tolerate the associated sedation. In a research trial he tried quetiapine, with the dosage adjusted up to 300 mg a day over ten days, but he did not like it. He reported feeling much better while taking haloperidol and has preferred to keep taking it even though he has been informed about its potential side effects, including tardive dyskinesia.
Mr. E is a 33-year-old Hispanic man who received a diagnosis of schizophrenia at the age of 21. He had been treated with various antipsychotic agents without improvement, but also without severe deteriorations that would have required hospitalization. Eight years after the onset of his illness, he started treatment with risperidone, reaching a dosage of 8 mg a day, and he showed some improvement in his psychotic symptoms. However, he developed tardive dystonia manifested by blepharospasm. The risperidone dosage was reduced to 2 mg a day, which caused Mr. E's psychotic symptoms to worsen without any improvement in his dystonic reaction.
Mr. E was then switched to quetiapine at an initial dosage of 200 mg a day. His tardive dystonic symptoms improved within two weeks, but his psychosis became worse. The quetiapine dosage was increased to 800 mg a day, but his psychosis still did not improve. At age 32, Mr. E was given thiothixene, and marked improvement in his symptoms was noted. He said he was feeling "almost normal." He started to become more socially active and started watching television, and he did not develop any dystonic reaction. He reported that he had not felt better with any of the new agents, and he refused to switch to any other medication. Mr. E's father confirmed the patient's improvement.
On the basis of an admittedly limited sample comprising the cases presented here and others, it appears that one major reason patients may resist switching from a conventional to an atypical antipsychotic is concern about "rocking the boat." Patients may fear decompensation and rehospitalization and thus view their present state as good enough and their side effects as tolerable—both better than the possible alternative.
This view should not be considered irrational. It can lead some patients to refuse to switch and others to abort a switch because of unexpected side effects or reemerging symptoms that may occur during the change. The patients described here had insight into their illness and their need for medications. In cases 3 and 5, family members agreed with the patient's decisions, believing that the patient was doing better with conventional agents.
Several recommendations emerge from these cases. First, education combined with serious consideration of the patient's concerns is necessary. Second, a careful switch may be necessary, perhaps with full overlap of therapeutic dosages of each agent to avoid reemerging symptoms. Careful attention to new or worsening side effects is also required. Third, the clinician may need to consider that the patient may be right. Although research based both on large groups and on case studies clearly shows the advantages of atypical antipsychotics, there is no evidence that such advantages are universal. A specific conventional antipsychotic may be more helpful for an individual patient than some atypical agents. Despite the general shift to the use of atypical agents, conventional antipsychotics remain an effective group of medications. Some patients may do better without switching or may need to switch back to a conventional agent.
From a medicolegal perspective, the reasons for keeping a patient on a conventional antipsychotic should be carefully documented. Records of discussions about side effects and variations in the risk of side effects with different antipsychotics should also be made, and periodic evaluations for movement disorders should be documented. Conventional antipsychotics appear to be associated with a much higher risk of tardive dyskinesia, which has been the subject of legal suits. Although we know of no legal cases resulting from the use of conventional antipsychotics as opposed to atypical agents, practitioners need to be cautious.
The authors are affiliated with the department of psychiatry and the behavioral sciences of the Keck School of Medicine at the University of Southern California in Los Angeles. Send correspondence to Dr. Kingsbury at the Keck School of Medicine, University of Southern California, 2020 Zonal Avenue, Los Angeles, California 90033 (e-mail, firstname.lastname@example.org). Dr. Simpson is editor of this column.
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