Neuroleptic-Induced Pseudo-Catatonia

Two contributions in the January edition of “Pharmacopsychiatry” deal with catatonic symptoms in psychiatric patients. One deals with the effects of treatment with risperidone [5], the other with catatonic symptoms in the course of benzodiazepine withdrawal [3]. Although the patients in both reports were treated with high doses of conventional antipsychotics (Table [1]), the possibility of a neuroleptic-induced pseudo-catatonia was, unfortunately, not even discussed as an alternative explanation for the “catatonic” symptomatology described.

Table 1 Medication of patients described as being catatonic (ba = before, aa = after admission) Medication Patient 1 5 Patient 2 3 Neuro-leptics Haloperidol 20 - 40 mg/d Benperidol 12 - 16 mg/d Haloperidol 6 mg/d (ba)Risperidone 4 mg/d (aa) Benzo-diazepines Lorazepam 5 mg Bromazepam 18 mg/d (ba)Lorazepam 3 mg/d (aa)

The issue of induction or exacerbation of psychotic symptoms by antipsychotics was first systematically raised by van Putten et al. [7], who described “phenothiazine-induced decompensation” in 9 of 80 schizophrenic patients. According to the author, this exacerbation was associated with “a subtle akathisia” and promptly responded to intramuscular biperiden. Brenner and Rheuban [1] described the “catatonic dilemma” in a 1978 case report addressing the difficulty of differentiating schizophrenic from pharmacogenic catatonic symptoms. Later, van Putten [8] extended his concept of “behavioral toxicity of antipsychotic drugs” to akinesia, which he defined as a “behavioral state of diminished spontaneity characterized by few gestures, unspontaneous speech and, particularly, apathy and difficulty with initiating usual activities”. Parallel to the symptoms of tardive dyskinesia that are well known for their exacerbation after dose reduction or withdrawal of antipsychotic medication and have been described in concurrence with “neuroleptic-induced supersensitivity psychosis” [2], other extrapyramidal symptoms such as parkinsonism also have been described [6]. A comprehensive review of mental side effects of neuroleptics, including a case report on “neuroleptic-induced pseudo-catatonia”, has recently been published in this journal [4].

What makes both case reports indicate the possibility of misdiagnosed “neuroleptic-induced pseudo-catatonia?

The patient presented by Hesslinger et al. is described as a 56-year-old male suffering from paranoid psychosis with delusions and depressive mood, possibly in combination with some brain damage (diffuse hyperdensity regions in the cCT). On admission in summer 1994 (premedication not given), he was described as being “in a state of (paroxysmal!) akinetic mutism with posturing and diaphoresis”, and the condition did not respond to benperidol 15 mg 4 times a day (a daily dose of 60 mg!) and lorazepam 20 mg/day. Since the condition did not change, the benperidol medication was changed to risperidone (up to 6 mg/day), and within a few days, the patient was reported to have become alert and able to walk spontaneously. Subjectively, the patient recollected that he had felt “as if he were buried”. Two relapses were reported to have occurred after tapering risperidone to 2 mg/d while he was an outpatient. Comment: Due to the age and suspected brain damage, this patient must have been regarded as being at special risk of extrapyramidal neuroleptic side effects. From a clinical point of view, a change of a paranoid psychosis into a catatonic form after 6 years of illness (1979 - 1986) is very unlikely. Unfortunately, no medication history before his admission in summer 1994 was reported. However, from clinical experience, it can be assumed that admission to the hospital was preceded by an increase in neuroleptic medication in an attempt to avoid hospitalization. An antipsychotic medication of 60 mg/d of benperidol is highly suspect as an inducer of severe extrapyramidal side effects in a risk patient. The description of the catatonic symptomatology as “paroxysmal” and its remission after change of antipsychotic medication to risperidone at 6 mg/d lend further support to the hypothesis that this “catatonic”symptomatology reflected a neuroleptic-induced pseudo-catatonia. Fluctuating neuroleptic plasma levels in the course of 4 daily oral doses of 15 mg of benperidol are certainly capable of inducing stuporous behavior, mutism, bizarre posturing, anorexia and intermittent diaphoresis as described by the authors. Also, a change to 6 mg/day of risperidone would result in a strong reduction of striatal dopamine D2-receptor blockade and thereby recovery from extrapyramidal symptomatology. The idea of neuroleptic pseudo-catatonia in the given case is further supported by the patient’s self-reported feeling of being “buried in a cave underneath the ground”. After remission of catatonic symptoms in the course of catatonic schizophrenia, patients mostly explain their bizarre behavior as driven by “external forces” such as voices, radiation or hypnosis. However, patients who experience neuroleptic side effects report that they feel as if they were “buried in a cave” without understanding what was going on or integrating the side effects into their delusions 4. The case report further states that following initiation of risperidone treatment, the patient has suffered “only two short relapses” - apparently without catatonic symptomatology - after risperidone dose reduction. This also indicates that he suffered from a neuroleptic-induced pseudo-catatonia induced by inappropriately high doses of high potency neuroleptics in the summer of 1994. The patient described by Deuschle and Lederbogen was described as a 51-year-old man who had been treated for a chronic condition with fatigue, insomnia and low performance with gradually increased doses of bromazepam that had reached 18 mg/day. After abruptly stopping his medication, the patient had developed psychotic symptoms (delusions, hallucinations) and severe agitation, and had therefore received haloperidol at 6 mg/d on two consecutive days. On day 5 after withdrawal (corresponding to day 1 after 2 days of haloperidol treatment that had - according to the authors - started on day 3 after abrupt withdrawal), he was described as “mute and ... posturing”. On admission, the patient was “mute” (but answered “with a few words at the beginning”), obviously anxious, and confirmed ideas of persecution and surveillance and acoustic hallucinations. He was further described as not showing spontaneous movements, posturing and having waxy flexibility without exhibiting excessive motor activity, echolalia or echopraxia. 4 hours after lorazepam (3 mg) and risperidone (4 mg) administration, the catatonic and psychotic symptomatology disappeared. Comment: In the discussion, both authors refer to the fact that “catatonia without delirium due to substance withdrawal” has so far only been reported after substance use of several classes or during benzodiazepine withdrawal in the elderly, in patients suffering from concurrent illnesses and treatments. They forget, however, that also their patient had “suffered from concurrent treatments”, namely haloperidol, at 6 mg on at least two consecutive days immediately before “catatonia” developed. It is therefore highly probable that this catatonic symptomatology reflected symptoms of haloperidol-induced acute dystonia that may have been intensified by abrupt benzodiazepine withdrawal. Like for the Hesslinger et al. case, administration of risperidone and lorazepam resolved all symptoms within 4 hours, which is - in combination with the appearance of symptomatology after 2 days of haloperidol treatment - indicative of a neuroleptic-induced pseudo-catatonia resulting from a reversible dopaminergic/cholinergic imbalance in basal ganglia circuits 4.

Since this discussion is based on information given from the 2 case reports, it cannot “prove” that the correct diagnosis would have been one of neuroleptic-induced pseudo-catatonia in either case, but there are a lot of facts pointing in this direction. Even if the authors are right in their assumptions, the possibility of neuroleptic side effects was not even mentioned in either discussion. This symbolizes the lack of awareness in the psychiatric community regarding the mental side effects of neuroleptics (including pseudo-catatonia). These side effects are therefore rarely diagnosed and treated correctly.

References

• 1 Brenner I, Rheuban W J. The catatonic dilemma.  Am J Psychiatry. 1978;  135 1242-1243
• 2 Chouinard G, Jones B D. Neuroleptic-induced supersensitivity psychosis: Clinical and pharmacological characteristics.  Am J Psychiatry. 1980;  137 16-21
• 3 Deuschle M, Lederbogen F. Benzodiazepine withdrawal - induced catatonia.  Pharmacopsychiatry. 2001;  34 41-42
• 4 Dose M. Recognition and management of acute neuroleptic-induced extrapyramidal motor and mental syndromes.  Pharmacopsychiatry. 2000;  33 (Supplement) 3-13
• 5 Hesslinger B, Walden J, Normann C. Acute and long-term treatment of catatonia with risperidone.  Phamacopsychiatry. 2001;  34 25-26
• 6 Nelli A C, Yarden P E, Guazzelli M, Feinberg I. Parkinsonism following neuroleptic withdrawal.  Arch Gen Psychiatry. 1989;  46 383-384
• 7 Van Putten T, Mutalipassi L R, Malkin M D. Phenothiazine-induced decompensation. Arch Gen Psychiatry 1974: 102-105
• 8 Van Putten T, Marder S R. Behavioral toxicity of antipsychotic drugs.  J Clin Psychiatry. 1987;  48 (Supplement 9) 13-19