Psychiatric Annals

Case Challenges 

A 44-Year-Old Man with a History of Schizoaffective Disorder

Branimir Margetić, MD; Branka Aukst-Margetić, MD, PhD

Abstract

Mr. A was a 44-year-old man with a 17-year history of a schizoaffective disorder, depressive type (according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition). He was a forensic patient hospitalized from 1998 to 2008. Until February 2010, he was on conditional release with the requirement of visiting an outpatient clinic once a month. He was prescribed haloperidol 10 mg/day, diazepam 20 mg/day, amitriptyline 100 mg/day, biperiden 6 mg/day, levomepromazine 100 mg/day, and haloperidol decanoate 100 mg/every 4 weeks. That treatment regimen was stable for more than 5 years.

Abstract

Mr. A was a 44-year-old man with a 17-year history of a schizoaffective disorder, depressive type (according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition). He was a forensic patient hospitalized from 1998 to 2008. Until February 2010, he was on conditional release with the requirement of visiting an outpatient clinic once a month. He was prescribed haloperidol 10 mg/day, diazepam 20 mg/day, amitriptyline 100 mg/day, biperiden 6 mg/day, levomepromazine 100 mg/day, and haloperidol decanoate 100 mg/every 4 weeks. That treatment regimen was stable for more than 5 years.

Branimir Margetić, MD, is with the Neuropsychiatric Hospital, Dr. Ivan Barbot, Popovac̆a, Croatia. Branka Aukst-Margetić, MD, PhD, is with the Psychiatric Clinic, University Hospital Center, Zagreb, Croatia.

Vlatka Boric̆ević Maršanić, MD, is with the Psychiatric Hospital for Children and Youth, Zagreb, Croatia.

Dr. Margetić, Dr. Aukst-Margetić and Dr. Boric̆ević Maršanić have disclosed no relevant financial relationships.

Address correspondence to: Branimir Margetić, MD, Neuropsychiatric Hospital, Dr. Ivan Barbot, Jelengradska 1, 44317, Popovac̆a, Croatia; fax 38544679005; or e-mail branimir.margetic@zg.t-com.hr.

Mr. A was a 44-year-old man with a 17-year history of a schizoaffective disorder, depressive type (according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition). He was a forensic patient hospitalized from 1998 to 2008. Until February 2010, he was on conditional release with the requirement of visiting an outpatient clinic once a month. He was prescribed haloperidol 10 mg/day, diazepam 20 mg/day, amitriptyline 100 mg/day, biperiden 6 mg/day, levomepromazine 100 mg/day, and haloperidol decanoate 100 mg/every 4 weeks. That treatment regimen was stable for more than 5 years.

In February 2010, his admission to the hospital was due to the reappearance of paranoid delusions of moderate intensity, because he was not compliant with the outpatient treatment and application of haloperidol decanoate the previous month, as had been recommended. Because the patient said that he had been taking all of his prescribed oral medications, it was believed that the intensification of paranoid delusions might be related to a lower dose of haloperidol. Therefore, on the day of admission, he received haloperidol decanoate, and all other mentioned medications were prescribed without any changes in their doses.

A day after admission, the patient became confused and disoriented. He did not know what year it was, could not remember where his room was, and his thoughts were incongruent. Each sentence had a normal structure, but their context had practically nothing in common. The patient showed impairment of attention and memory, had no insight into his condition, and was showing moderate excitement and anxiety. After 11 days, all mentioned signs, which were most prominent 24 to 48 hours after admission, had disappeared, and the patient was able to say that his use of the medications was irregular, “as needed.”

During that period, his sleep, food, and liquid intakes were normal. The routine laboratory tests (a complete blood count, sodium, potassium, glucose, liver enzyme, creatine phosphokinase, and urine tests) were normal, his blood pressure was 120/70 to 130/85 mm Hg, his pulse rate 72 to 84 beats/min, and his temperature was normal. He was not agitated, had no hallucinations, or any gastrointestinal and extrapyramidal signs, and skin and mucous membranes were normally hydrated. Accordingly, the patient was not in a life-threatening situation.

It became evident, a few days after admission, that the condition was improving. The conclusion was that the patient’s condition was related to the sudden increase of plasma concentrations of drugs. However, it was decided to proceed with current medications without any changes in their dosing.

Diagnosis

Delirium

Delirium may be precipitated by virtually any psychotropic drug, but drugs with anticholinergic properties and benzodiazepines may cause delirium more frequently. The approach to the condition should be the cessation of treatment or the lowering of the dose of the offending drug.1 However, because of polypharmacy, clinicians sometimes are not able to manage this condition in such simple ways.

Discussion

All prescribed drugs might have an influence on the development of delirium,2 but the cessation of treatment with practically all drugs used here can lead to a range of discontinuation symptoms,3 including potentially life-threatening conditions.4,5 The patient told us that he had been taking the medications. In such circumstances, clinicians must believe in information given by the patient, although on the second day after admission, it became obvious that this information was highly questionable. The main and still unresolved question is what to do in similar situations.

Of note, we had no capacities to analyze drug concentrations in the plasma, but it is also questionable whether that could be of help in making a decision. The patient was already treated with the same doses of all of these drugs during a previous hospitalization, and at that time, there were no signs of confusion. Therefore, there was no reason to believe that the toxic concentrations in plasma are the cause of the condition.

Our assumption, most probably confirmed by the outcome, was that these signs were related to the suddenly increased concentrations of drugs with anticholinergic activity (antipsychotics, amitriptyline, biperiden), although the patient’s absence of peripheral manifestations of anticholinergic excess was striking. Animal studies have shown that chronic administration of the cholinergic antagonist scopolamine6 and haloperidol7 may induce the up-regulation of the muscarinic receptors. Accordingly, it is possible that the patient could tolerate the medications during chronic administration but could not tolerate suddenly increased cholinergic blockade with drugs in doses he previously tolerated. A speculative postulation may be that about 11 days were needed for the up-regulation of the muscarinic receptors and for maintaining physiologic homeostasis. This conclusion should be taken cautiously, especially because the patient was treated with haloperidol and diazepam. These drugs might be therapeutic and may prevent the development of delirium.8

However, during the first days after admission, delirium was not the only diagnosis being considered. Confusion could be a sign of the development of the serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS).9 Accordingly, stopping all or some medications, due to the longest half-life of haloperidol decanoate, could be accompanied by a loss of anticholinergic and probably a benzodiazepine protective role that could lead to NMS.

On the other hand, various benzodiazepines, some antipsychotics (including haloperidol), and the 5-HT2 blockers (eg, methysergide) have been described as therapeutic for SS.9 Of note, levomepromazine is a low-potency aliphatic phenothiazine antipsychotic characterized by strong sedative abilities and a 5-HT2A:D2 affinity ratio of 5:1.10

Therefore, the question was, is it more appropriate to proceed with the current treatment or to stop giving the patient all or some of his medications? If the answer was just to stop giving him some of his medications, the question was, what medications would they be, and when would they be stopped? There is no clear answer to that question. Moreover, one may well imagine that the use of specific “anticholinergic antidotes” (eg, physostigmine) could clarify the diagnosis. It is the fact that intravenous administration of these drugs can result in prompt, but only temporary, clearing of the delirium.11 However, in this case, the patient was not in a life-threatening situation, and there were no signs of peripheral manifestations of anti-cholinergic excess. An alternative diagnosis (especially at the beginning) was the development of NMS. Therefore, it was decided not to use anticholinergic antidotes.

The approach that consisted of close monitoring of the patient’s condition, with special attention directed to the possible development of symptoms more specific to anticholinergic toxicity, SS, or NMS, without cessation of treatment, proved to be successful.

Conclusion

This remains an illustrative case of a questionable approach that, initially, was based on misleading information from a patient. It also emphasizes the need for special attention during the use of polypharmacy. Finally, there is a lack of data related to the development of tolerance to medications with anticholinergic properties in clinical settings. This case suggests that, in certain circumstances, tolerance can be developed in about 11 days.

References

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  7. Pazo JH, Rascovsky S, Jerusalinsky D, Medina JH, Tumilasci OR. Increase of muscarinic cholinergic receptors in the rat submandibular glands after parasympathectomy and repeated administration of haloperidol. Gen Pharmacol. 1989;20(6):759–761.
  8. Markowitz JD, Narasimhan M. Delirium and antipsychotics: a systematic review of epidemiology and somatic treatment options. Psychiatry (Edgmont). 2008;5(10):29–36.
  9. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol. 1999;13(1):100–109. doi:10.1177/026988119901300111 [CrossRef]
  10. Shiloh R, Nutt D, Weizman A. Atlas of Psychiatric Pharmacotherapy [revised ed.]. London, UK: Martin Dunitz; 2000:48–57.
  11. Eyer F, Jetzinger E, Pfab R, Zilker T. Withdrawal from high-dose tranylcypromine. Clin Toxicol (Phila). 2008;46(3):261–263.
Authors

Branimir Margetić, MD, is with the Neuropsychiatric Hospital, Dr. Ivan Barbot, Popovac̆a, Croatia. Branka Aukst-Margetić, MD, PhD, is with the Psychiatric Clinic, University Hospital Center, Zagreb, Croatia.

Vlatka Boric̆ević Maršanić, MD, is with the Psychiatric Hospital for Children and Youth, Zagreb, Croatia.

Dr. Margetić, Dr. Aukst-Margetić and Dr. Boric̆ević Maršanić have disclosed no relevant financial relationships.

Address correspondence to: Branimir Margetić, MD, Neuropsychiatric Hospital, Dr. Ivan Barbot, Jelengradska 1, 44317, Popovac̆a, Croatia; fax 38544679005; or e-mail .branimir.margetic@zg.t-com.hr

10.3928/00485713-20100902-02

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