APPROACH TO EMERGENCIES IN SCHIZOPHRENIA
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Psychiatria Danubina, 2018; Vol. 30, Suppl. 4, pp S203-207 Conference paper
© Medicinska naklada - Zagreb, Croatia
APPROACH TO EMERGENCIES IN SCHIZOPHRENIA
IN UNIVERSITY HOSPITAL "VRAPýE"
Ante Siliü, Aleksandar Saviü, Ilaria ýulo, Suzana Kos, Jakša Vukojeviü,
Daška Brumen & Draženka Ostojiü
University Psychiatric Hospital Vrapþe, Zagreb, Croatia
SUMMARY
Background: An emergency in psychiatric setting is any disorder in thought process, feelings and/or behavior of the patient that
requires urgent therapeutic intervention. In general, we can observe an increase in numbers of psychiatric emergencies throughout
the world and in Croatia as well. Agitation and aggression are one of the most common causes of emergency in psychiatry. Agitation
is common and frequent in patients suffering from schizophrenia. Patient can be agitated in various levels such as: mild, moderate or
severe and can alternate between these levels in the same presentation. Agitated patients often require hospitalization that includes
pharmacotherapy and sometimes physical restraining, in order to treat the cause of agitation and prevent auto and/or
heterodestructive behavior.
Subjects and methods: In this paper we focus on patients suffering from schizophrenia that were admitted in University Hospital
"Vrapþe" in 2017, and assess the numbers through the criteria of voluntary vs. involuntary admissions and physical restraint usage.
Results: Out of total observations, 130 (35.6%) were patients admitted for the first time and 179 (49%) were patients later
diagnosed with schizophrenia spectrum and other psychotic disorders. Court ordered involuntary hospitalization was ordered for 35
(2.8%) patients out of total admitted patients, and 68.6% (N24) of them were diagnosed with schizophrenia spectrum and other
psychotic disorders. Physical restraint was used for 122 patients out of total admissions and 28.7% (N35) of restrained patients were
diagnosed with schizophrenia spectrum and other psychotic disorders.
Conclusions: Emergencies in patient suffering from schizophrenia are extremely delicate and demanding situations in every-day
clinical practice of psychiatrist. There is an increased risk involved for the patient but for the staff as well. All interventions should
be individualized and patient should carefully monitored throughout the entire process. All professionals involved in care for a
patient should be up to date with medical and legal issues.
Key words: schizophrenia - psychotic disorders - psychomotor agitation - violence
* * * * *
INTRODUCTION these visits (Sankaranarayanan & Puumala 2000, Marco
& Vaughan 2005). 52% of presented patients in the
An emergency in psychiatric setting is any disorder Psychiatric ER were agitated and 45% of them were
in thought process, feelings and/or behavior of the hospitalized and received specific psychopharmaco-
patient that requires urgent therapeutic intervention. In therapy in order to reduce agitation (Boudreaux 2009).
general, we can observe an increase in numbers of Schizophrenia spectrum and other psychotic disorders
psychiatric emergencies throughout the world and in are grouped together in recent classifications - DSM 5
Croatia as well (Ostojiü & ýulo 2018, Siliü 2018). Agi- (American Psychiatric Association 2013). Psychiatry
tation and aggression are one of the most common cau- redefined the term “psychosis” in numerous occasions
ses of emergency in psychiatry. Agitation is common so far and it is safe to say that we did not achieve
and frequent in patients suffering from schizophrenia. generally accepted definition (Sadock et al. 2015). In
Patient can be agitated in various levels such as: mild, context of emergencies in psychiatry we can define psy-
moderate or severe and can alternate between these chosis as a disturbance of the perception of reality which
levels in the same presentation. Agitated patients often may or may not include hallucinations and delusions.
require hospitalization that includes pharmacotherapy We can define delusions as false, fixated beliefs and
and sometimes physical restraining, in order to treat the hallucinations as sensory perceptions (in all sensory
cause of agitation and prevent auto and/or hetero- modalities) in the absence of real external stimuli.
destructive behavior (Allen 2000, Allen & Currier 2004). Neither hallucinations nor delusions should be consi-
Agitation is always related to the underlying disease and dered as diagnosis rather as a symptom (Goldberg &
when patient presents with agitation we always have to Murray 2006, Gelder et al. 2007, Black & Andreasen
consider the possible cause such as schizophrenia, bi- 2014). Every psychotic patient should be approached to
polar disorder, substance abuse disorders, iatrogenic etc as having a potential for psychiatric emergency whether
(Buckley 2006, Leventhal & Zimmerman 2010, Fioren- it is patient’s first or repeated contact with psychiatric
tini et al. 2011). Data from the United States (US), services. Differential diagnostic procedures should be
suggests close to two million emergency department started as soon as possible in order to clarify the patho-
visits per year that involve agitated patients, with physiology and etiology underlying presented symp-
schizophrenia being an underlying cause for 21% of toms. All psychotic patients must be monitored closely
S203Ante Siliü, Aleksandar Saviü, Ilaria ýulo, Suzana Kos, Jakša Vukojeviü, Daška Brumen & Draženka Ostojiü: APPROACH TO EMERGENCIES IN
SCHIZOPHRENIA IN UNIVERSITY HOSPITAL "VRAPýE" Psychiatria Danubina, 2018; Vol. 30, Suppl. 4, pp 203-207
during their evaluation. Not all psychotic patients will Out of total observations, 130 (35.6%) were patients
become agitated and can be treated without difficulties, admitted for the first time and 179 (49%) were patients
but we should anticipate and when possible prevent later diagnosed with schizophrenia spectrum and other
agitated and violent outbursts routinely in a manage- psychotic disorders.
ment of psychotic patient. Agitation is very often Court ordered involuntary hospitalization was orde-
preceded by verbal or behavioral hints but may also red for 35 (2.8%) patients out of total admitted patients,
emerge without warning (Sadock et al. 2015). and 68.6% (N24) of them were diagnosed with schizo-
Diagnostic and therapeutic decisions should be made phrenia spectrum and other psychotic disorders.
in good clinical practice manner by a team of educated Physical restraint was used for 122 patients out of
professionals. All involved professionals (psychiatrists, total admissions and 28.7% (N35) of restrained patients
nurses…) should be up to date with medical and legal were diagnosed with schizophrenia spectrum and other
aspects of care for management of psychiatric emergen- psychotic disorders. Every physically restrained patient
cies (Allen et al. 2005). In medicine in general there are diagnosed with schizophrenia spectrum and other psy-
few clinical situations that can be as complicated as are chotic disorders was administered with parenteral the-
those emerging with management of psychotic patients. rapy in the acute setting (within 48 hours upon admis-
During the process of management of each individual sion). We used haloperidol, olanzapine, promazine and
psychotic patient we must achieve delicate balance bet- ziprasidone i.m and/or diazepam i.m. (Table 1).
ween care (intervention) and safety of the patient and
staff while respecting patient’s human rights. Recog- DISCUSSION
nizing and preventing violent behavior is one of the
most important priorities in psychiatric emergencies According to our data, diagnosis of schizophrenia
(Chanmugam et al. 2013). spectrum and other psychotic disorders was strong
predictor of need for involuntary treatment if patient did
SUBJECTS AND METHODS not give valid informed consent upon admission and not
a strong predictor for usage of physical restraint.
In this paper we focus on patients suffering from Here we state some clinical facts and recommenda-
schizophrenia that were admitted in University Hospital tions based on our experience and available guidelines.
„Vrapþe“ in 2017, and assess the numbers through the
criteria of voluntary vs. involuntary admissions and Clinical facts crucial to recognition and avoidance
physical restraint usage. We analyzed data on file in of violent behavior (Savic 2018)
retrospective manner. It is difficult to predict violent behavior but it is most
often related to:
RESULTS x Intoxication with alcohol or other psychoactive
substances (Alkhouri et al. 2010);
In 2017, total number of admissions in University x Neuro cognitive disorders such as dementia,
hospital “Vrapþe” was 7.167. Out of total admissions, delirium or brain injuries;
2.244 (31.3%) were diagnosed with schizophrenia spec- x Schizophrenia spectrum and other psychotic
trum and other psychotic disorders. Number of admis- disorders;
sions in Department for urgent psychiatry was 1.235. x Personality disorders.
Number of patients that were admitted for the first time
was 579 (46.9%) and number of patient that were admit- Patient must be approached in a calm manner:
ted (and discharged) prior to 2017 was 656 (53.1%). x Involved professional must not present in intimi-
439 (35.5%) admitted patients were discharged with dating, authoritative or provoking manner;
diagnosis of schizophrenia spectrum and related psycho- x Clinician must address patient quietly from a
sis. Out of total admissions 870 (70.4%) valid informed “passive position” while respecting personal space
consents were obtained during admission process and of the patient which can be wider than usual in a
365 (29.6%) patients were admitted for the observation psychotic patient – usually two arm lengths;
(up to 48 hours), according to Croatian law for psychia- x Neither clinician nor patient must not feel “cor-
tric patients – ZZODS (Kos 2018). nered”.
Table 1. Analysis of total number of admissions in Department for Urgent psychiatry in 2017
Total no of admissions First admission Repeated admission Sch* - admission Observation Observation-first
1235 (7167) 579 656 439 365 130
46.9% 53.1% 35.5% 29.6% 35.6%
Sch-observation Court** Court - sch Restraint Restraint - sch Perenteral – sch
179 35 24 122 35 35
49% 2.8% 68.6% 9% 28.7% 100%
*schizophrenia spectrum and other psychotic disorders; **court ordered involuntary hospitalization
S204Ante Siliü, Aleksandar Saviü, Ilaria ýulo, Suzana Kos, Jakša Vukojeviü, Daška Brumen & Draženka Ostojiü: APPROACH TO EMERGENCIES IN
SCHIZOPHRENIA IN UNIVERSITY HOSPITAL "VRAPýE" Psychiatria Danubina, 2018; Vol. 30, Suppl. 4, pp 203-207
Table 2. Advantages and disadvantages of different routes of administration (adopted from Zeller et al. 2016)
Administration Time to peak plasma
Advantages Disadvantages Examples
route concentration
Intramuscular Rapid systemic entry; Invasive; can damage Haloperidol ~20 minutes
patient cooperation not patient - physician Olanzapine 15–45 minutes
necessary relationship Aripiprazole* 1–3 hours
Ziprasidone 60 minutes
Inhaled Less invasive than Requires patient cooperation Loxapine* 2 minutes
intramuscular route and can Bronchospasm/ respiratory
improve patient experience. distress
Enters alveoli for rapid entry
into arterial circulation
Oral
Standard Less invasive than Require patient cooperation; Haloperidol 2–6 hours
tablets/ intramuscular route and can slow onset of action; enter Olanzapine 5–8 hours
capsules/ improve patient experience systemic circulation via Risperidone ~1 hour
solution portal system resulting in Aripiprazole 3–5 hours
potential for erratic Ziprasidone 6–8 hours
absorption; can be diverted
(“cheeking”)
Orally Less invasive than intra- Slow onset of action; enter Olanzapine ~6 hours
disintegrating muscular route and can systemic circulation via Risperidone 1–2 hours
tablets improve patient experience. portal system resulting in Aripiprazole 3–5 hours
Less potential for diversion potential for erratic
(“cheeking”) vs standard absorption
tablets/capsules; suitable for
patients with dysphagia
Buccal/ Less invasive than intra- Requires patient coopera- Sublingual 0.5–1.5 hours
sublingual muscular route and can tion; needs to be taken asenapine*
improve patient experience; correctly so that it is not
rapid absorption; swallowed, mitigated in part
avoids first-pass metabolism by the friability of the tablet
Intranasal Less invasive than intra- Requires patient Intranasal 10 minutes
muscular route and can cooperation. midazolam*
improve patient experience;
rapid absorption;
avoids first-pass metabolism
* Currently not available in Croatia
Table 3. Other psychopharmacs that can be used in Clinician should calmly ask the patient “What seems
emergencies in patient suffering from schizophrenia to be wrong?” or “What is going on?” or state “You
spectrum and other psychotic disorders (Stahl 2014) seem to be angry, can I know why?....”
Group Target symptoms Violent patients need to be hospitalized because in
Antiepileptic / mood stabilizer Positive symptoms that way we can ensure their safety and safety of
Na-valproate Agitation people surrounding them.
Carbamazepine Aggression If and when needed violent or agitated patient should
Lamotrigine Negative symptoms be restrained according to good clinical practice and
Topiramate Affective symptoms law (ZZODS).
Gabapentine Underlying cause of psychotic symptoms should be
Lithium intensively treated.
Benzodiazepines Agitation Outpatients should be reassessed for violent behavior
Diazepam Anxiety on every visit.
Clonazepam Insomnia Therapeutic interventions in management of agita-
Lorazepam tion in patient suffering from schizophrenia can be sum-
Alprazolam marized in two groups: behavioral (non-pharmacolo-
Bromazepam gical) and pharmacological (Zeller & Citrome 2016).
Oxazepam
Flurazepam Behavioral intervention
Midazolam Verbal de-escalation – should be attempted with all
Nitrazepam patients.
S205Ante Siliü, Aleksandar Saviü, Ilaria ýulo, Suzana Kos, Jakša Vukojeviü, Daška Brumen & Draženka Ostojiü: APPROACH TO EMERGENCIES IN
SCHIZOPHRENIA IN UNIVERSITY HOSPITAL "VRAPýE" Psychiatria Danubina, 2018; Vol. 30, Suppl. 4, pp 203-207
Quiet unlocked room - patients in whom de-escala- First line therapy in acute setting can be inhaled Lo-
tion alone was insufficient to reduce dangerousness enough xapine. Loxapine is a first-generation antipsychotic struc-
to allow to remain in general care areas, and/or may need turally similar to clozapine. Recommended dosage via
more time to regain control away from other patients inhalation (approved by FDA for agitation in schizo-
Locked seclusion - if patients are considered an immi- phrenia and manic phase of bipolar disorder) is 10 mg
nent danger to others but not themselves, and cannot and should not be exceeded through 24 hours. It can be
tolerate or remain in a quiet unlocked room. administered only for in patients (Keating 2013, Popovic
Restraint - if patients are considered an imminent et al. 2015). At this moment Loxapine is not available
danger to themselves, and cannot remain in a locked in-patient.
seclusion room without actively trying to injure them- In psychiatric emergencies with agitated or violent
selves. behavior in addition to antipsychotic we can administer
parenterally benzodiazepines such as lorazepam (cur-
Non pharmacological interventions should be prefer- rently not available in-patient in parenteral formulation)
red but there are some advantages and disadvantages or diazepam (Beckman & Haas 1980, Citrome 2013).
of such interventions for agitation (Saviü 2018)
Recommendations on dosages and combinations of
Advantages: facilitates better short- and long-term drugs are not generally accepted but there are some gene-
patient–physician relationships, reduces staff and patient ral rules (Gugger 2011, Citrome 2013, Huang et al. 2015):
injuries associated with restraint and sedation and can All drug to drug interactions should be considered as
reduce resource (clinical and staff) use. well as possible interactions with psychoactive sub-
Disadvantages: may not be effective in all patients stances on individual basis;
and most importantly it requires at least some co-opera- We must not exceed maximal recommended daily
tion from the patient. dose;
Pharmacological intervention Simultaneous administration of parenteral formula-
tion of olanzapine and any benzodiazepine is not
First line of treatment in psychiatric emergencies is
allowed;
psychopharmacotherapy. Mechanism of action is pri-
If i.m. therapy does not achieve desired effect, ex-
marily blockage of dopamine D2 receptors in meso-
ception can be made and it is possible to administer
limbic projections of dopaminergic neurons. That effect
slow intravenous application of haloperidol or dia-
in cascade reaction leads to psychomotor calming of the
zepam with rigorous monitoring of vital functions.
patient in the acute phase of treatment but is also
important in the long run. (Zeller & Citrome 2016, Given the heterogeneity of presentation in psychia-
Saviü 2018). tric emergencies in schizophrenia patients, we can be
faced with necessity of administering other group of
Antipsychotic drugs represent highly heterogeneous
psychopharmacs (Ostojiü et al. 2017, Siliü 2017).
group of drugs interacting with various types of recep-
tors other than dopaminergic (serotoninergic, cholinergic,
noradrenergic, histaminergic…) (Fruyt & Demyttenaere CONCLUSIONS
2004, Zeller & Rhoades 2010).
Emergencies in patients suffering from schizophrenia
Which drug will be drug of choice in psychiatric
spectrum and related psychoses are extremely delicate
emergencies depends on various factors:
and demanding situations in every-day clinical psychia-
Leading symptom(s): auto or heterodestructive beha-
tric practice. There is an increased risk involved for the
vior, hallucinations, delusions, anxiety, agitation,
patient but for the staff as well. All interventions should
insomnia…
be individualized, carefully timed and patient should
Potential side effects: EPS, sedation, hypotension, carefully monitored throughout the entire process. All
QT effect… professionals involved in care for a patient should be up
Earlier response to therapy; to date with medical as well as with legal issues involved.
Earlier developed side effects;
Psychiatric and non psychiatric co morbidities;
What patient prefers (when possible, respecting Contribution of individual authors:
patient’s wishes regarding formulation, brand-name
and type of therapy can lead to better long-term Ante Siliü: conception and design of the paper, ana-
lysis and interpretation of data;
outcomes).
Aleksandar Saviü: conception and design, participa-
Whenever it is possible we should administer mono- ted in drafting and revising article;
therapy. Combining two or more drugs is often neces- Ilaria ýulo & Suzana Kos: analysis and interpretation
sary but should be avoided if possible. There are diffe- of data, critical revision;
rent formulations of psychopharmacotherapy available Jakša Vukojeviü: analysis and interpretation of data,
for the management of emergencies in schizophrenia. data search
We should always prefer peroral route of administration Daška Brumen: acquisition of data;
if possible thus avoiding intrusive ways of admini- Draženka Ostojiü: conception and design, participated
stering a drug (Ostinelli et al. 2017). in drafting and revising article.
S206Ante Siliü, Aleksandar Saviü, Ilaria ýulo, Suzana Kos, Jakša Vukojeviü, Daška Brumen & Draženka Ostojiü: APPROACH TO EMERGENCIES IN
SCHIZOPHRENIA IN UNIVERSITY HOSPITAL "VRAPýE" Psychiatria Danubina, 2018; Vol. 30, Suppl. 4, pp 203-207
randomized controlled trial. J Formos Med Assoc 2015;
Acknowledgements: None. 114:438-45
18. Keating GM: Loxapine inhalation powder: a review of its
Conflict of interest: None to declare. use in the acute treatment of agitation in patients with bi-
polar disorder or schizophrenia. CNS Drugs 2013; 27:479-89
19. Kos S: Zakonski okviri zbrinjavanja hitnih stanja u
References psihijatriji (Croatian laws on management of emergencies
in psychiatry). In Jukiü V & Ostojiü D (eds): Hitna stanja u
1. Allen MH: Managing the agitated psychotic patient: a psihijatriji, 125-30. Medicinska naklada, Klinika za
reappraisal of the evidence. J Clin Psychiatry 2000; psihijatriju Vrapþe, 2018
61(S14):11-20 20. Leventhal AM & Zimmerman M: The relative roles of
2. Allen MH & Currier GW: Use of restraints and phar- bipolar disorder and psychomotor agitation in substance
macotherapy in academic psychiatric emergency services. dependence. Psychol Addict Behav 2010; 24:360-5
Gen Hosp Psychiatry 2004; 26:42-9 21. Marco CA & Vaughan J: Emergency management of agita-
3. Allen MH, Currier GW, Carpenter D, Ross RW & Docherty tion in schizophrenia. Am J Emerg Med 2005; 23:767-76
JP: Expert Consensus Panel for Behavioral Emergencies 22. Ostinelli EG, Brooke-Powney MJ, Li X & Adams CE: Halo-
2005. The expert consensus guideline series. Treatment of be- peridol for psychosis-induced aggression or agitation (rapid
havioral emergencies. J Psychiatr Pract 2005; 11(S1):5-108 tranquillization). Cochrane Database Syst Rev 2017; 7
4. Alkhouri I, Gibbons P, Ravindranath D & Brower K: 23. Ostojiü D & ýulo I: Hitni psihijatrijski bolesnik - agitacija i
Substance-Related Psychiatric Emergencies. In: Riba MB & agresija (Emergency in psychiatry – agitation and
Ravindranath D (eds): Clinical Manual of Emergency aggression). In Jukiü V & Ostojiü D (eds): Hitna stanja u
Psychiatry. Washington, DC, London, England: American psihijatriji, 18-30. Medicinska naklada, Klinika za
Psychiatric Publishing, 2010 psihijatriju Vrapþe, 2018
5. American Psychiatric Association: Diagnostic and 24. Ostojiü D, Siliü A, Kos S, ýulo I & Saviü A: Terapija prve
statistical manual of mental disorders (5th ed.). Arlington, psihotiþne epizode (Treatment of First episode psychosis).
VA: American Psychiatric Publishing, 2013 Medicus 2017; 26:151-60
6. Beckman H & Haas S: High dose diazepam in schizo- 25. Popovic D, Nuss P & Vieta E: Revisiting loxapine: a
phrenia. Psychopharmacology (Berl) 1980; 71:79-82 systematic review. Ann Gen Psychiatry 2015; 14:15
7. Black DW & Andreasen NC: Introductory textbook of 26. Sadock BJ, Sadock VA & Ruiz P: Kaplan & Sadock's
Psychiatry. 6th ed. American Psychiatric Publishing, 2014 Synopsis of Psychiatry. 11th ed. Wolters Kluwer, 2015
8. Boudreaux ED, Allen MH & Claassen C: The psychiatric 27. Sankaranarayanan J & Puumala SE: Epidemiology and
emergency research collaboration - 01: methods and characteristics of emergency departments visits by US
results. Gen Hosp Psychiatry 2009; 31:515-22 adults with psychiatric disorder and antipsychotic mention
9. Buckley PF: Prevalence and consequences of the dual from 2000 to 2004. Curr Med Res Opin 2007; 23:1375-85
diagnosis of substance abuse and severe mental illness. J 28. Saviü A: Naþini procjene rizika i primjena intervencija
Clin Psychiatry 2006; 67(S7):5-9 (preventivnih/deeskalacijskih, farmakoterapijskih) (Risk
10. Chanmugam A, Triplett P & Kelen G: Emergency assessment and interventions – preventive/de-escalation,
psychiatry. Cambridge University Press, 2013 pharmacotherapy). In Jukiü V & Ostojiü D (eds): Hitna
11. Citrome L: Limited evidence of effects of haloperidol alone stanja u psihijatriji, 78-87. Medicinska naklada, Klinika za
for rapid tranquilization in psychosis-induced aggression. psihijatriju Vrapþe, 2018
Evid Based Ment Health 2013; 16:47 29. Siliü A: Hitna stanja kod psihotiþnih bolesnika (Emer-
12. Fiorentini A, Volonteri LS & Dragogna F: Substance- gencies in psychotic patients). In Jukiü V & Ostojiü D (eds):
induced psychoses: a critical review of the literature. Curr Hitna stanja u psihijatriji, 51-60. Medicinska naklada,
Drug Abuse Rev 2011; 4:228-40 Klinika za psihijatriju Vrapþe, 2018
13. De Fruyt J & Demyttenaere K: Rapid tranquilization: new 30. Siliü A: Psihofaramakoterapijske specifiþnosti u lijeþenju
approaches in the emergency treatment of behavioral prvih psihotiþnih poremeüaja (Psychopharmacotherapy
disturbances. Eur Psychiatry 2004; 19:243-9 specificities in treating first episodes of psychotic
14. Gelder M, Harrison P & Cowen P: Shorter Oxford Text- disorders). In: Ostojiü D (ed): Suvremeni pristup prvim
book of Psychiatry. 5th ed. Oxford University Press, 2007 psihotiþnim poremeüajima, 49-56. Zagreb: Medicinska
15. Goldberg D & Murray R: The Maudsley Handbook of Prac- naklada, Klinika za psihijatriju Vrapþe, 2015
tical Psychiatry. 5th ed. Oxford University Press, 2006 31. Stahl SM: Stahl's essential psychopharmacology. Pre-
16. Gugger JJ: Antipsychotic pharmacotherapy and orthostatic scriber's guide. 5th ed. Cambridge university press, 2014
hypotension: identification and management. CNS Drugs 32. Zeller SL & Citrome L: Managing Agitation Associated
2011; 25:659-71 with Schizophrenia and Bipolar Disorder in the Emergency
17. Huang CL, Hwang TJ, Chen YH, Huang GH, Hseih MH, Setting. West J Emerg Med 2016; 17:165-72
Chen HH et al.: Intramuscular olanzapine versus intra- 33. Zeller SL & Rhoades RW: Systematic reviews of assessment
muscular haloperidol plus lorazepam for the treatment of measures and pharmacologic treatments for agitation. Clin
acute schizophrenia with agitation: An open-label, Ther 2010; 32:403-25
Correspondence:
Ante Siliþ, MD, PhD
University Psychiatric Hospital VrapĀe
BolniĀka cesta 32, 10 000 Zagreb, Croatia
E-mail: ante.silic@gmail.com
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