Short reports
Antipsychotic drug-induced acute
laryngeal dystonia: two case reports
and a mini review
Christos Christodoulou Athens’ General Hospital ‘G. Gennimatas’, Psychiatric Department, Greece.
Chryssanthi Kalaitzi Athens’ General Hospital ‘G. Gennimatas’, Psychiatric Department, Greece.
Abstract
Antipsychotic-induced laryngeal dystonia is a life-threatening side-effect
of both high- and low-potency classical antipsychotics, and its diagnosis
often remains elusive. We review all cases of acute laryngeal dystonia
due to antipsychotics available in the literature, including controversial
ones, and add two new cases. There are no reports of acute laryngeal
dystonia due to atypical antipsychotics. Antipsychotic-induced laryngeal
dystonia has been reported predominantly in young males, but does not
correlate to the dosage or the category of the drug. There have been
reports of acute laryngeal dystonia due to metoclopramide. Differential
Introduction
In many previous studies, sudden death in psychiatric patients has
been related to the use of phenothiazines. Most of the cases
referred to physically healthy individuals receiving phenothiazines
for various psychiatric disorders, predominantly schizophrenia.
Autopsy findings concerning the reason for death were inconclu-
sive. Clinical observations attributed death either to regurgitation
and asphyxiation or to cardiotoxicity (Holister and Kosek, 1965;
Leestma and Koeing, 1968; Solomon, 1977).
Other studies have described acute laryngeal–pharyngeal
dystonia as the possible cause of respiratory distress, and have
considered it as the possible cause of some unexplained deaths
relating to antipsychotics (Flaherty and Lahmeyer, 1978; Mann et
al., 1979; Menuck, 1981).
With the introduction of atypical antipsychotics, further efforts
to investigate the issue stopped because phenothiazines appeared
to be out-of-date. As far as we know, there are no reports of laryn-
geal dystonia caused by atypical antipsychotics. Nevertheless,
classical antipsychotics continue to represent a significant percent-
age of the prescribed antipsychotics, particularly in chronic
patients (Mossman and Lehrer, 2000; Rey, 2002), ethnic minorities
(Kuno and Rothbard, 2002; Opolka et al., 2004) and countries with
less wealthy economies (Hosak and Bahbouh, 2002; Knapp et al.,
2002; Weissman and Essock, 2002; Apiquian et al., 2004).
Corresponding author: Chryssanthi Kalaitzi, Dekelias 5, Neo Heraklio, 14122, Athens, Greece. Email: ckalaitzi@yahoo.gr
Journal of Psychopharmacology
19(3) (2005) 307–312
© 2005 British Association
for Psychopharmacology
ISSN 0269-8 8 1 1
SAGE Publications Ltd,
London, Thousand Oaks,
CA and New Delhi
10.1177/0269881105051543
diagnosis includes other extrapyramidal side-effects and allergic
reactions. Treatment consists of the administration of anticholinergic
agents.
Keywords
acute laryngeal dystonia, antipsychotic-induced laryngeal dystonia,
antipsychotic side-effects, thioridazine
We report two cases of acute laryngeal dystonia in patients who
were receiving antipsychotics and review all of the cases of acute
laryngeal-pharyngeal dystonia reported to date.
The aim of this short report is to familiarize clinicians with the
characteristic symptoms of this life-threatening syndrome, in
which diagnosis often remains elusive.
Case report
Case 1
The patient was a 28-year-old man who was referred to our consul-
tation–liaison psychiatry services 1 day after admission to the
orthopedic clinic of our hospital for multiple fractures, after having
fallen from a height under the influence of auditory hallucinations.
Psychotic symptoms begun approximately 7 days before his sui-
cide attempt. No psychopathology had been noticed previously,
nor had the patient ever received any psychotropic medication. He
had recently moved to Athens from his hometown to find work and
was facing many difficulties in adjusting to a new lifestyle.
After the first evaluation, he was prescribed 5 mg haloperidol,
4 mg biperiden HCl and 6 mg diazepam daily. The patient was hos-
pitalized to the orthopedic clinic for 9 days and then transferred to
the psychiatric clinic. Haloperidol was raised to 15 mg daily and
308 Antipsychotic drug-induced acute laryngeal dystonia
biperiden HCl to 6 mg daily. The day after the last increase of the
dosage, he experienced severe extrapyramidal side-effects (muscle
rigidity, retrocollis, oculogyric crisis, opisthotonos, pronounced
cogwheeling, etc.). The potential for acute laryngeal dystonia was
considered to be serious, and haloperidol was therefore withdrawn.
The patient continued to receive biperiden HCl for the next 2 days
and was then switched to a low potency antipsychotics (thiori-
dazine, 200 mg daily).
Twenty days after his admission to the psychiatric department,
the patient was discharged showing marked improvement, with
instructions to follow the aforementioned regimen. Preliminary
diagnosis was schizophrenia-like psychosis. On follow-up, the
patient’s cooperation was suboptimal. Five months later, he relapsed,
and the dosage was increased to 300 mg thioridazine daily. The
final diagnosis was schizophrenic disorder of paranoid type.
One month after the last increase of thioridazine, he presented
to the emergency department with severe respiratory distress,
grasping his throat with his hands. His condition was fluctuating in
severity, causing devastating symptoms for approximately 30 s and
milder symptoms for the following 2 min. When he improved, he
complained, in a harsh voice, of extreme difficulty in breathing.
Inspection of the oral cavity was unremarkable. His lips were
slightly cyanotic. No other extrapyramidal or dystonic signs were
present. His blood pressure was 110/70 mmHg and his heart rate
was 110 b.p.m. The diagnosis of laryngeal dystonia was suspected
based on the clinical presentation and on the previous history of
other extrapyramidal side-effects when he was receiving haloperi-
dol. He was given 5 mg biperiden lactate i.m., which improved the
situation. Ten minutes later, he was given another 5 mg of biperi-
den i.m. and the dystonia resolved. The patient revealed later that
he took 800 mg of thioridazine (4 × 200 mg) 4 h before admission
in an attempt to relieve his anxiety.
Case 2
The patient was a 35-year-old woman who preseneted to the emer-
gency department of our hospital with acute respiratory distress
and laryngeal striddor. She was married, worked as an English
professor and had a history of schizophrenia, but had stopped her
medication for over 3 months.
She was in severe distress, sweaty and profoundly dyspnoic.
Her voice was hoarse and, periodically, she had difficulty both
breathing and talking. There was also laryngeal striddor. Her symp-
toms were progressively deteriorating, although still intermittent.
Her blood pressure was 135/80 mmHg and her heart rate was
120 b.p.m. An electrocardiogram proved normal, apart from a
benign supraventricular tachycardia, consistant with her somatic
distress. She had no other extrapyramidal symptoms. The rest of
her physical and laboratory investigation was unremarkable.
She was referred to an otorhinolaryngologist. Laryngoscopy
confirmed the presence of intermittent dystonic movements of the
laryngeal musculature, with no oedema in the region. Emergency
room staff were preparing for an intubation.
The psychiatrist proposed the possibility of antipsychotic-
induced laryngeal dystonia (despite the fact that the patient denied
taking antipsychotics) and the patient was given 10 mg biperiden
lactate i.m. She gradually improved. Her symptoms resolved
fully within 30 min but she remained in the hospital for further
investigation.
As proven subsequently, after the patient stopped her medica-
tion, her psychosis had relapsed and she experienced persecutory
delusion and auditory hallucinations with poor insight, thus refus-
ing any medication. On the advice of a psychiatrist, and to sedate
her for admission to a psychiatric hospital, her mother had secretly
put 50 drops of haloperidol (10 mg/ml) in the patient’s meal 1 h
before the appearance of the symptoms.
Discussion
Mini review
Since the introduction of antipsychotics for the treatment of
psychiatric disorders in 1952, there have been several reports of
antipsychotic-related deaths. The pathophysiological mechanisms
considered to underlie these deaths were: (i) acute cardiac arrest
due to dysrhythmia, hypotension or both and (ii) regurgitation
resulting in acute asphyxiation (Holister and Kosek, 1965;
Leestma and Koeing, 1968). Nonetheless, the exact causes of death
remain obscure because all autopsies proved inconclusive.
Peele and Loetzen (1973) questioned the term ‘phenothiazines
death’, stating that this term refers to two already well-known
causes of sudden deaths with no characteristic autopsy findings:
(i) death due to cardiac arrest that is no different to the entity
described in the general population and (ii) the lethal catatonia of
the mentally ill (Peele and Loetzen, 1973)
In the present study, we review the literature on laryngeal–
pharyngeal dystonia and describe the symptoms characterizing this
entity. To the 24 cases reported in the international literature to
date, we add the two verified cases that we have come across
during 17 years of working in the psychiatric department of a gen-
eral hospital (the first one in 1991 and the second in 2002). All
cases that have ever been reported are presented in Table 1.
Clinical characteristics
Based on the above, one can safely conclude that very few individ-
uals receiving antipsychotics will develop acute laryngeal dysto-
nia. A total of 26 patients have been reported to date. Of these, five
cases were inadequately substantiated, and their validity is in ques-
tion (Christian and Paulson, 1958; Waugh and Metts, 1960; Flaherty
and Lehmeyer, 1979; Kock and Pi, 1989). Furthermore, three deaths
have been reported (Ketai et al., 1979; Weiner, 1979; Modestin et
al., 1981), all concerning middle-aged women receiving haloperi-
dol. In only one of those cases was death formally attributed to acute
laryngeal dystonia (Modestin et al., 1981). On the other hand,
experienced clinicians fear that the diagnosis of this side-effect is
often elusive and that many of the unexplained deaths of psychi-
atric patients could be due to antipsychotic-induced laryngeal
dystonia (Mann et al., 1979; Menuck, 1981; Koek and Pi, 1989).
 Antipsychotic drug-induced acute laryngeal dystonia 309

Table 1 Summary of all of the reported cases of antipsychotic-induced laryngeal dystonia

Case Age Gender Psychiatric diagnosis Agent Reference

1a† 20 Male – Prochlorperazine Christianand Paulson (1958)

2a 21 Female – Prochlorperazine Waugh and Metts (1960)
3 49 Male Paranoia vera Fluphenazine ethanate Solomon (1977)
4 28 Male Acute psychosis Haloperidol Flaherty and Lahmeyer (1978)
5 39 Male Schizophrenia Haloperidol Flaherty and Lahmeyer (1978)
6a NA NA NA NA Mann et al. (1979)
7a NA NA NA NA Mann et al. (1979)
8a NA NA NA NA Mann et al. (1979)
9† 35 Female Acute psychosis Haloperidol Ketai et al. (1979)
10† 43 Female Acute psychosis Haloperidol Weiner (1979)
11 21 Male Alcohol abuse, aggressive behaviour Haloperidol Menuck (1981)
12 19 Male Bipolar disorder, manic phase Thiothixine Ravi et al. (1982)
13† 44 Female schizophrenia Haloperidol Modestin et al. (1981)
14 16 Male None (vomiting) Metoclopramide + prochlorperazine Newton-John (1988)
15 35 Male None (vomiting) Metoclopramide Newton-John (1988)
16 29 Male Bipolar disorder, manic phase + chlorpromazine Koek and Pi (1989)
substance abuse
17 25 Male Schizoaffective disorder + Haloperidol Koek and Pi (1989)
substance abuse
18 Late twenties Male Schizophrenia Haloperidol Stevens (1990)
19 14 Male Chloropromazine overdose Chlorpromazine + fluoxetine Murrey (1996)
20 16 Male Chloropromazine overdose Chlorpromazine Russel et al. (1996)
22 24 Male Schizophrenia Haloperidol Ilchef (1997)
19 26 Woman Schizophrenia Haloperidol Fines et al. (1999)
23 10 Male None Metoclopramide Tait (2001)
24 26 Female Schizophrenia Chlorpromazine + haloperidol + Lanzaro et al. (2001)
zuclopentixol
25 28 Male Schizophrenia Thioridazine Our patient (2004)
26 35 Female Schizophrenia Haloperidol Our patient (2004)

aCase inadequately substantiated. †Fatal outcome. NA, Not available.

Acute laryngeal dystonia presents with dyspnoea, laryngeal
striddor and extreme distress. The patient’s hands are characteristi-
cally grabbing his/her throat (Flaherty and Lahmeyer, 1978; Mann
et al., 1979;, Menuck, 1981; Koek and Pi, 1989). Dystonic reac-
tions may be present in other parts of the body, such as the head,
neck or pharynx (Stevens, 1990; Murrey, 1996; Lanzaro et al., 2001)
and there have also been cases of generalized dystonia (Mann et al.,
1979; Koek and Pi, 1989). In both our cases, laryngeal–pharyngeal
dystonia was the only symptom, as was the case in many other
reports. (Flaherty and Lahmeyer, 1978; Mann et al., 1979; Menuck,
1981; Ravi et al., 1982; Koek and Pi, 1989) Moreover, dystonia
was intermittent in both cases.
Differential diagnosis
The possibility of an allergic reaction should always be included in
our differential diagnosis (Ilchef, 1997) Nevertheless, this was not
the case with our first patient because there were no other signs or
symptoms of an allergic reaction, there was no history of allergy,
the patient was not receiving any other medication and the symp-
toms subsided with anticholinergic agents. In our second case,
laryngoscopy ruled out the possibility of an allergic reaction. This
case was rather more difficult because the patient denied having
taken any medication. It was only the high suspicion of the psychi-
atrist that saved her from a needless and potentially dangerous
intubation.
Another entity that must be taken into consideration in the dif-
ferential diagnosis of such patients is laryngeal tardive dyskinesia
(Feve et al., 1995), which presents with tardive dyskinetic
phenomena in the laryngeal and pharyngeal muscles and causes
difficulties in speaking, breathing and swallowing. Usually, tardive
dyskinesia signs also exist in other parts of the patient’s body.
None of the above was true for our patient, although, once more,
the therapeutic success of anticholinergics makes tardive dyskine-
sia rather unlikely. For the same reason, we excluded respiratory
dyskinesia, an entity characterized by irregular rhythm, frequency
and depth of breathing. It has been described exclusively in
patients’ suffering from tardive dyskinesia (Chiu et al., 1992).
Airway obstruction of any aetiology cannot be the cause in
such cases because the symptoms subside with anticholinergic
medication.
The absence of fever, the normal vital signs, as well as the nor-
mal level of consciousness in a person under antipsychotics who
presents with abnormal muscle rigidity, all exclude the diagnosis of
malignant neuroleptics syndrome. This is supported by the rapid
resolution of symptoms after administering anticholinergic agents.
310 Antipsychotic drug-induced acute laryngeal dystonia
Risk factors
The majority of the cases of acute laryngeal dystonia present in
males aged under 30 years (Flaherty and Lahmeyer, 1978; Menuck,
1981; Ravi et al., 1982; Newton-John, 1988; Koek and Pi, 1989;
Stevens, 1990; Murrey, 1996; Russel et al., 1996; Ilchef, 1997). It
is well established that young males show an increased incidence
of acute dystonic reactions during the first days of high-potency
antipsychotic therapy (Swett, 1975; Flaherty and Lahmeyer, 1978;
Settle and Ayd, 1983). Acute laryngeal dystonia also appears to
develop more frequently in young males receiving high potency
antipsychotics (Flaherty and Lehmeyer, 1979). All major cate-
gories of the classical antipsychotics, namely butyrophenones
(Flaherty and Lahmeyer, 1978; Menuck, 1981; Modestin et al.,
1981; Koek and Pi, 1989; Stevens, 1990; Fines et al., 1999),
phenothiazines (Newton-John, 1988; Koek and Pi, 1989; Murrey,
1996; Russel et al., 1996) and thioxanthenes (Ravi et al., 1982)
have been related to acute laryngeal dystonia. Furthermore, there
have been two reported cases of acute laryngeal dystonia caused
by metoclopramide (Newton-John, 1988; Tait, 2001). To our
knowledge, our first case was the first example of acute laryngeal
dystonia due to thioridazine overdose to be reported.
In most cases of laryngeal dystonia, antipsychotics dosage
varied from low to average (Flaherty and Lahmeyer, 1978;
Menuck, 1981; Ravi et al., 1982; Koek and Pi, 1989). Therefore,
when assessing the risk of developing acute laryngeal dystonia, the
possibility of an idiosyncratic hypersensitivity to the extrapyrami-
dal side-effects of antipsychotics must be taken into consideration
(Koek and Pi, 1989). Hypersensitivity to antipsychotics is indica-
tive of a higher risk of developing acute dystonia in the future
(Swett, 1975; Settle and Ayd, 1983). In our first case, dystonia was
dose-dependant, as was the case in previous reports (Flaherty and
Lahmeyer, 1978; Russel et al., 1996). Of the three deaths reported
in verified cases of antipsychotic drug-induced laryngeal dystonia,
two were in women who were receiving large doses of haloperidol
(Ketai et al., 1979; Modestin et al., 1981). The first one received
140 mg of haloperidol on the day before her death and 80 mg on
the day she died (Ketai et al., 1979). The second woman received
60 mg of haloperidol intramuscularly and 60 mg per o.s. on the day
before her death and 100 mg per o.s. on the day of death, which
was attributed to laryngeal–pharyngeal dystonia (Modestin et al.,
1981). However, in the third case, dosage did not exceed 25 mg of
haloperidol (Weiner, 1979).
In some of the previously reported cases, patients suffered from
severe commorbid disorders, such as alcoholism (Menuck, 1981),
hyperthyroidism (Weiner, 1979), mononucleosis (Newton-John,
1988), AIDS (Newton-John, 1988), uremia (Koek and Pi, 1989)
and pneumonia (Koek and Pi, 1989). Some authors claim that
hyperthyroidism favours the neurotoxic effects of haloperidol
(Weiner, 1979), whereas many other disorders are considered to
predispose to neurological dysfunction (Koek and Pi, 1989).
Implications for clinical care
Acute laryngeal dystonia can be fatal, unless doctors maintain a
high suspicion index. Early recognition can save lives. Patients
presenting with intermitting dyspnoea who have a history of men-
tal disorders, regardless of whether they are aware that they are
taking antipsychotics, should be regarded as suffering from acute
laryngeal dystonia and treated accordingly. Laryngeal striddor and
concurrent dystonic reactions in other parts of the body also
indicate acute laryngeal dystonia.
Differential diagnosis includes acute anaphylaxis, tardive
laryngeal dystonia, airway obstruction and respiratory dyskinesia.
Diagnosis can be confirmed by laryngoscopy, which reveals inter-
mittent dystonic movements of the laryngeal musculature, with no
oedema in the region.
In all cases (Flaherty and Lahmeyer, 1978; Mann et al., 1979;
Menuck, 1981; Ravi et al., 1982; Newton-John, 1988; Koek and Pi,
1989; Stevens, 1990; Fines et al., 1999; Murrey, 1996) dystonic
symptoms subsided using anticholinergic agents parenterally.
Diphenhydramine HCl, both i.m. and i.v., benzotropine i.v. (but not
i.m.; Ravi et al., 1982; Koek and Pi, 1989), procyclidine i.v. and
biperiden lactate i.m. have all been used with success. There is no
evidence that benzodiazepines are necessary for the treatment of
antipsychotic drug-induced laryngeal dystonia. Anticholinergics
appear to suffice and, unlike benzodiazepines, they do not compro-
mise respiration.
All classical antipsychotics can cause acute laryngeal dystonia,
including low-potency antipsychotics. Acute laryngeal dystonia
usually develops at the beginning of the antipsychotic therapy or a
few days after an increase in dosage. Regardless of whether the
patient will require long-term addition of anticholinergics in the
therapeutic scheme, such medication should be prescribed for
the aforementioned periods of therapy (4–7 days). In addition, all
patients who have experienced dystonic reactions when under
classical antipsychotics should be switched to atypical agents,
especially if they are young males or suffer from chronic severe
somatic diseases. Furthermore, patients receiving typical antipsy-
chotics, as well as their families, should be informed of this poten-
tially life-threatening side-effect. If dyspnoea develops, patients
should be instructed to take anticholinergic agents (preferably
5 mg of biperidine lactate) and present as a a matter of urgency at
the nearest hospital.
Conclusion
Antipsychotic drug-induced laryngeal dystonia is a rarely reported,
but potentially life-threatening side-effect of classical antipsy-
chotics and can easily be misdiagnosed. All clinicians dealing with
patients who are receiving antipsychotics, as well as those pre-
scribing metoclopramide, must be aware of the characteristic
symptoms of laryngeal dystonia, particularly acute intermitted
dyspnoea, which is usually accompanied by dystonia in other parts
of the body. The relationship between acute laryngeal dystonia and
unexplained sudden death in patients receiving antipsychotics
needs further investigation.
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