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Journal of Clinical Pharmacy and Therapeutics, 2015, 40, 699–701 doi: 10.1111/jcpt.

12330

Case Report
Zolpidem test and catatonia

H. Javelot* PharmD, PhD, B. Michel† PharmD, PhD, R. Steiner‡ MD, T. Javelot§ MD and O. Cottencin¶ MD, PhD
*Clinical Pharmacy Service – Mental Health Establishment (EPSAN), Brumath, †Faculte de Pharmacie – Laboratoire HuManiS (EA 7308), Service Pharmacie –
CHU de Strasbourg, Strasbourg, ‡Service G06, Mental Health Establishment (EPSAN), Brumath, §Equipe de Liaison et de Soins en Addictologie, Centre
Hospitalier Saint Jean de Dieu, Lyon, and ¶Department of Psychiatry and Addiction Medicine, Fontan 2 Hospital, University Hospital of Lille, University of
Lille, CHU de Lille, Lille, France

Received 27 August 2015, Accepted 7 October 2015

Keywords: catatonia, paranoid schizophrenia, zolpidem, zolpidem test

SUMMARY CASE DESCRIPTION


What is known and objective: There is no consensus regarding Mr. S., 32 years old, was hospitalized as a result of a catatonic
treatment of catatonia and the main recent therapeutic progress episode. His past medical history included paranoid schizophre-
has been the development of the zolpidem diagnostic and nia, of more than 10-year duration and stabilized for several
therapeutic test. We report on the use of this test in one of our years with 225 mg/day of olanzapine, and with enuresis
patients. treated with imipramine. Upon admission at our psychiatric
Cases summary: Mr. S. suffered from a paranoid schizophrenia. inpatient unit, his general condition had worsened: he had lost
Three episodes of catatonia are described to illustrate the effect several kilos in weight and had severely stiff joints and a stupor
of zolpidem in a patient for whom lorazepam was ineffective or interspersed with moments of agitation. Hyperthermia suggested
inadequate. a possible neuroleptic malignant syndrome (NMS) that required
What is new and conclusion: Zolpidem with appropriate testing a transfer to an emergency department for aetiological assess-
appears to be a credible alternative to electroconvulsive therapy ment and refeeding. The NMS diagnosis was rejected because
or increased lorazepam dosing and allows continuation of the patient presented with a slight elevation of creatine
antipsychotic administration. phosphokinase (CPK) and a urinary infection which was treated
with amoxicillin. The extrapyramidal rigidity improved with
tropatepine (10 mg/2 mL, IM) combined with 10 mg zolpidem
WHAT IS KNOWN AND OBJECTIVE
orally 3 times a day. Mr. S. agitation was controlled, but he was
Catatonia is a rare and spectacular syndrome that results from still anxious as a result of auditory verbal hallucinations and
poor psychomotor functioning characterized by a loss of delirious ideas. Once his condition had improved, he returned to
coherent motor initiative. There is no consensus regarding the the psychiatric department following 11 days of treatment on a
most appropriate treatment, but the use of antipsychotics, as combined daily dose of 20 mg of tropatepine, 30 mg of
first-line treatment, is now considered dangerous due to the zolpidem, 15 mg of lorazepam and 10 mg of olanzapine. His
risk of malignant progression.1–3 Reference treatments in the condition fluctuated during the day, with, in particular, partial
literature are electroconvulsive therapy (ECT) and benzodi- but fleeting symptomatic regression after meals. Within 3 days,
azepines,1,2 with lorazepam considered to be the most effec- Mr. S. was once more able to feed himself, his contact was
tive.1,4 The main therapeutic progress achieved recently has better, and his movements were more spontaneous. Two days
been the development of the zolpidem diagnostic and thera- later, he was able to walk again. The dose of zolpidem was
peutic test, which has been reported to provide symptomatic reduced the following day and then stopped after 48 h.
improvement,5,6 and for predictions to be made on the likely Two months later, catatonia re-appeared with psychotic
response to lorazepam. To date, only a few cases have been recrudescence. The doses of lorazepam and tropatepine were
reported.7–11 The main obstacle to such use of zolpidem is the raised to 625 mg per day and 30 mg per day, respectively,
transient nature of its effects, giving rise to an ‘on/off’ effect whereas olanzapine was replaced with 15 mg per day of
directly linked to the plasma concentration5 and requiring aripiprazole, and increased to 30 mg daily 1 month later. Zolpi-
several doses per day. However, a positive effect has been dem was reintroduced at a daily dose of 30 mg. There was a
reported after 1 year of treatment.8 partial improvement in the catatonic syndrome, associated with
The following report concerns a clinical case that illus- frequent manifestations of psychosis. Aripiprazole, which was
trates different aspects of the use of zolpidem as a diagnos- ultimately deemed to be ineffective, was replaced with 4 mg of
tic and therapeutic tool, a still relatively unexplored risperidone. After 2 weeks, catatonia became more fluctuating,
intervention. worse or better depending on whether Mr. S was clinically
observed or alone, or occupied with close friends and family,
respectively. Zolpidem was then discontinued and the dose of
Correspondence: Dr H. Javelot, Clinical Pharmacy Service – Mental lorazepam upped to 75 mg per day. His condition continued to
Health Establishment (EPSAN), Brumath, France. Tel.: +33(0)388 646 improve over the following 2 months. After 6 months in hospital,
170; fax: +33(0)388 646 158; e-mail: herve.javelot@ch-epsan.fr he was finally discharged.

© 2015 John Wiley & Sons Ltd 699


Zolpidem test and catatonia H. Javelot et al.

The following 2 years were characterized by deficient-mode identifiable organic cause. However, they raise questions on the
psychotic decompensation with the reappearance of catatonic longitudinal diagnosis of paranoid schizophrenia in the context of
symptoms, requiring several long spells in hospital. He was the DSM-IV-TR. The inclusion of catatonia in DSM as a clinical and
diagnosed as having an underactive thyroid, which was treated evolving form of schizophrenia, a disorder connected with a
with L-thyroxine. Fifteen months after his first admission to general medical condition or a characteristic associated with a
hospital, and following frequent falls, he broke the horizontal plate mood disorder, has been criticized, in particular by Taylor and
of his jawbone. During a further spell in hospital, several drugs Fink, who propose a refined syndromic and aetiopathogenic
were tried in succession, all to no avail: antipsychotics (amisul- approach to catatonia.2 The question about the stability of
pride, olanzapine, pimozide) and antiepileptic drugs (topiramate). longitudinal diagnoses (i.e. paranoid schizophrenia versus cata-
His background treatment with lorazepam varied between 75 and tonic schizophrenia) can be a difficult one to address whether such
15 mg per day. Ten months later, he suffered a catatonic relapse diagnoses are used to ascertain the best type and duration of
despite being on a daily dose of 75 mg of lorazepam and 300 mg pharmacological treatment. The fact that Mr. S had been taking
of amisulpride. He was then put back on a daily 30 mg dose of antipsychotic medication for 10 years, which the guidelines are
zolpidem, which led once again to a maximum fluctuation in unable to assess, raises the question of iatrogenesis.15
negativism at meal times, dropping off postprandially and in the The existence of residual or recurring catatonic symptoms
evening, with an improvement in behaviour and contact. Amisul- following an NMS has also been described.16,17 This raises the
pride was replaced with 10 mg of olanzapine. The improvement question of an individual susceptibility common to these two
continued despite a persistent slight deficient symptomatology. scenarios, especially in clinical practice.18 Cycloid or periodic
Zolpidem was gradually discontinued over a 10-day period. A motor activity psychoses are currently being researched with a
year later, the patient’s clinical condition remains stable, with no view to investigating any genetic predisposition common to these
repeat of catatonic episodes. disorders.19,20
When patients take their antipsychotic medications regularly, the
prognostic for paranoid schizophrenia is usually good. However,
WHAT IS NEW AND CONCLUSION
although our patient had been stabilized for 10 years, he had several
catatonic episodes without returning to his former self. The reintroduction of zolpidem in our patient’s treatment when he
The initial episode suggested NMS: (two A criteria: intense experienced his second and third catatonic episodes means
muscle rigidity and elevated temperature associated with the use zolpidem can be regarded as an adjuvant therapy for background
of neuroleptic medication, and several B criteria: changes in level treatment with lorazepam which can produce greater therapeutic
of consciousness, leukocytosis, mutism, incontinence and labora- efficiency in a patient still being treated with antipsychotic
tory evidence of muscle injury as a result of elevated CPK).12 medication given the persistence of a productive symptomatology.
Nonetheless, here hyperthermia, probably linked to a urine During the third episode, the differential effect of the zolpidem on
infection, may have caused physical stress while on antipsychotic the background treatment with lorazepam is still apparent,
treatment. The catatonic episodic appeared secondary to a general although the ensuing regression of symptoms is not as marked
medical condition in the context of schizophrenia. In this particular as during the initial decompensation.
clinical case, the chronology makes diagnosis difficult and This case report is therefore an illustration of how a large dose
required the need to administer different specific treatments (30 mg/day) of zolpidem can be used as an adjuvant to lorazepam
simultaneously, raising the possibility of a secondary self-induced for treating recurring catatonic episodes. The diagnostic and
catatonic state and the worsening of the pre-existing disturbance. therapeutic test with zolpidem seems to be a credible alternative
The link between catatonia and NMS has been the subject of many to increasing the doses of lorazepam, thus avoiding a relay by
different hypotheses.3 The most popular hypothesis suggests that high doses of lorazepam which, unlike zolpidem, always carries
NMSis an iatrogenic form of lethal catatonia, with risk factors13 that the risk of respiratory depression. Adding zolpidem to lorazepam
include high dose antipsychotic (225 mg/day of olanzapine) in may also be an alternative to ECT and permit the continued
combination with an antidepressant (imipramine used to treat administration of antipsychotics in a patient whose productive
enuresis); current catatonic manifestations; dehydration and hydro- symptomatology requires it.
electrolyte imbalances; and prodromes14 (prodromal phase of anorexia
and insomnia; hyperactive phrase, with mutism, catalepsy and
ACKNOWLEDGEMENTS
rigidity, interspersed with periods of paradoxical agitation and with
hyperthermia). Our patient presented with the latter clinical picture. The authors want to express their gratitude to the translators, Mrs
The introduction of zolpidem seems to have played a specific Gillian Beeton-Wakenhut (conference interpreter).
role in improving the patient’s catatonia, but with systematic
postprandial regression of symptoms, even when the antipsychotic
CONFLICT OF INTEREST
was re-introduced. Conversely, and by analogy, the recrudescence
of negativism before meal times evokes end-of-dose fluctuations.5 All the authors of this article attest that there was no potential
Following episodes were simple catatonic episodes of variable conflict of interest that could have influenced this work.
intensity, with the absence of any general medical condition or

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