CNS Drugs 2009; 23 (3): 193-212

REVIEW ARTICLE 1172-7047/09/0003-0193/$49.95/0

ª 2009 Adis Data Information BV. All rights reserved.

Management of Patients Presenting with

Acute Psychotic Episodes of Schizophrenia
Pierre Thomas,1 Köksal Alptekin,2 Mihai Gheorghe,3- Mauro Mauri,4 José Manuel Olivares5 and
Michael Riedel 6
1 Department of Psychiatry, University of Lille Medical School, Lille, France
2 Department of Psychiatry, School of Medicine, Dokuz Eylul University, Izmir, Turkey
3 Department of Psychiatry, Clinical Central Military Hospital, Bucharest, Romania
4 Department of Clinical Psychiatry, University of Milan, Milan, Italy
5 Department of Psychiatry, Vigo University Hospital, Pontevedra, Spain
6 Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany

Contents
Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
1. Management of Acute Psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
2. Treatment Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
3. Management Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
4. Standard Paradigm for Management of Typical Relapses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
4.1 The First 4 Days . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
4.2 The First 4 Weeks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
5. Highly Agitated Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
5.1 The First 4 Days . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
5.2 The First 4 Weeks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
6. First-Episode Psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
6.1 The First 4 Days . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
6.2 The First 4 Weeks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
7. Patients at High Risk of Suicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
7.1 The First 4 Days . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
7.2 The First 4 Weeks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
8. Patients Presenting with Drug Intoxication and Withdrawal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
8.1 The First 4 Days . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
8.2 The First 4 Weeks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
9. Elderly Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
10. Special Issues Related to Gender . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
11. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206

Abstract The initial management of patients with schizophrenia presenting to psy-

chiatric emergency departments with an acute psychotic episode requires rapid
decisions to be made by physicians concerning the treatment of individuals
who are likely to be relatively uncooperative, agitated and lacking insight.
The treatment decision must be adapted to the individual characteristics and

- Deceased.
194 Thomas et al.

needs of each patient. This article reviews the issues from the perspective of
the initial management of acute psychosis as it is currently practised in Europe,
and discusses the pragmatic implications for initial treatment decisions and
the elaboration of a long-term treatment plan. Initially, administration of
antipsychotics to control psychotic symptoms and benzodiazepines to con-
trol agitation represents the cornerstone of treatment. Oral medication is
preferable to injectable forms wherever possible, and atypical antipsychotics
are to be preferred over conventional agents because of their lower risk of
extrapyramidal adverse effects, which are a major determinant of poor ad-
herence to treatment. Whatever antipsychotic is chosen by the physician
during the initial period, it is likely that it will need to be continued for many
years, and it is thus important to take into account the long-term safety
profile of the drug chosen, particularly in relation to extrapyramidal adverse
effects, metabolic complications and quality of life. Building a therapeutic
alliance with the patient and his/her family or carers is an important element
that should be included in the initial management of psychosis. The long-term
goal should be to minimize the risk of psychotic relapse through adequate
treatment adherence.

1. Management of Acute Psychosis implications for initial treatment decisions and

The initial management of patients with schizo-
phrenia presenting to psychiatric emergency
departments with an acute psychotic episode
requires rapid decisions to be made by physicians
about which treatments are most suitable for
treating a patient who is likely to be relatively
uncooperative, agitated and lacking insight. The
decisions that are made in such a situation have
important consequences for the likelihood of
success of maintenance therapy once the patient
returns to the community and thus on the pre-
vention of future psychotic relapses. In a number
of countries, professional associations have de-
veloped guidelines and treatment algorithms for
the initial management of acute psychosis[1-10]
with the aim of optimizing both the short-term
treatment response and the long-term outcome.
The relative importance of the issues underlying
these recommendations varies from patient to
patient, depending on clinical presentation, psy-
chiatric and treatment antecedents, the structure
of care in the community, and the extent of family
support and awareness. This article reviews
these issues from the perspective of the initial
management of acute psychosis as it is currently
practised in Europe, and discusses the pragmatic
the elaboration of a long-term treatment plan.
2. Treatment Objectives
Treatment objectives for the initial manage-
ment of acute psychotic episodes are multiple. In
the short term, these objectives consist of rapid
control of symptoms, particularly agitation and
psychotic symptoms, and prevention of harm to
the patient or others. Prevention of harm includes
reducing suicide risk, self-harm, domestic and
public accidents, hostility and assaults, and
the medical complications of any co-morbidity.
Subsequent treatment goals include establishing
and consolidating a therapeutic alliance with the
patient and family, ensuring a smooth transition
to maintenance treatment, and establishing a
plan to optimize adherence to treatment.[11] The
relative priority given to these different goals may
differ according to the specific characteristics of
each patient. For example, harm prevention is
critical in patients with antecedents of suicide
attempts or suicidal ideation. In first-episode
patients, informing the patient and family and
establishing a therapeutic alliance is a specific,
and particularly important, issue.

ª 2009 Adis Data Information BV. All rights reserved. CNS Drugs 2009; 23 (3)
Management of Acute Psychosis
3. Management Strategies
Initial management of acute psychosis needs
to take into account the specific needs, ante-
cedents and prognosis of each individual patient.
In addition, interventions need to evolve over
time as symptoms of psychosis resolve with
treatment. In this article, we consider different
patient profiles, starting with a general descrip-
tion of issues for care in a patient presenting with
a ‘typical’ psychotic relapse and then describing
the specific issues associated with particular pa-
tient groups (table I). We discuss strategies for the
short- and medium-term initial management of
acute psychosis. Short-term management refers
to the first 4 days, which is the period during
which it should be possible to gain control over
symptoms and stabilize the patient. Medium-
term management refers to the time from the end
of the short-term period out to 4 weeks, during
which period the state of the patient still needs to
be followed closely and a maintenance treatment
plan conceived and put in place.
4. Standard Paradigm for Management
of Typical Relapses
This section discusses the management of
previously treated patients regardless of the seve-
rity of the psychotic symptoms but without major
agitation (characterized by behavioural hyper-
activity, anxiety, tenseness, verbal aggressiveness
and risk of harm to self or others) and who do not
present any special treatment considerations (e.g.
relevant somatic or psychiatric co-morbidities,
addictions or old age). In general, such patients
can be treated on an open ward or as outpatients,
since they are sufficiently lucid and cooperative
to participate in treatment decisions and do not
require constant attention. Such patients re-
present over half of all cases of relapse seen in
psychiatric practice.[10,12-14]
4.1 The First 4 Days
On admission, it is important to carefully as-
certain the nature and severity of the relapse and
to exclude alternative diagnoses such as drug-
ª 2009 Adis Data Information BV. All rights reserved.
195
induced psychosis. The patient’s medical records
should be scrutinized and the patient’s entourage
interviewed about previous psychotic episodes,
response to treatment, and compliance. The pa-
tients should be examined to detect other poten-
tial somatic and psychiatric co-morbidities,
which will need to be taken into account in the
treatment choice.
In these patients, it is important to set up
communication channels with the patient from
the very beginning in order to construct solid
foundations for a future therapeutic alliance.
This involves informing the patient of the need
for immediate and long-term treatment and
stressing the importance of adherence to a treat-
ment plan. The patient’s attitudes and beliefs
with respect to treatment should be carefully in-
vestigated and taken into account in the choice of
treatment. The family should also be involved in
building the therapeutic alliance, as their support
will be essential in maintaining treatment ad-
herence and in identifying early warning signs
of relapse once the patient returns to the home
environment.
If anxiety or agitation is present, benzodiaze-
pines should be given immediately to calm the pa-
tient.[15] The dose of benzodiazepine chosen should
be based on the degree of agitation. Lorazepam
and alprazolam are the benzodiazepines of choice
for this purpose. Appropriate use of benzodiaze-
pines in the immediate phase allows the agitation
of the patient to be controlled satisfactorily before
the introduction of antipsychotic treatment. In
patients with sleep disturbances, use of non-
benzodiazepine hypnosedatives (zopiclone, zolpi-
dem or zaleplon) can be considered.
Time should be taken over choosing the most
appropriate antipsychotic drug based on the pre-
vious experience of the patient, the adverse effect
profile of the drugs and the planned transi-
tion into maintenance therapy. The antipsychotic
drug chosen should be considered suitable for
both the acute and maintenance phase without
the need for a switch in treatment. It should be
recognized firstly that every medication switch
prolongs the inpatient stay and, secondly, that it
is by no means guaranteed that antipsychotics
will be able to maintain symptom control and
CNS Drugs 2009; 23 (3)
ª 2009 Adis Data Information BV. All rights reserved.

196
Table I. Specific features and issues associated with particular groups of patients with acute psychosis
Parameter Typical relapse Highly agitated First episode High suicide risk Drug intoxication Elderly
Proportion (%) »50 »10–15 <10 Unknown Unknown »15
Key features No need for confinement Agitation No previous diagnosed Antecedents of Acute drug Risk of impaired
Previous experience of Need for confinement antecedents of psychosis suicide attempts intoxication cognitive function
antipsychotic drugs Low insight or Suicidal ideation or withdrawal Altered sensitivity to
Sufficient insight to compliance Confused state antipsychotic drugs
participate in treatment at admission
choice
No relevant co-morbidities

Key management Building therapeutic alliance Identify the nature Differential diagnosis Need for dose Control of Differential diagnosis
issues Improving treatment and cause of History taking observation intoxication or vs dementia
adherence agitationa Use of atypical Therapeutic alliance withdrawal Antipsychotic dose
Selecting antipsychotic Rapid control of antipsychotics and family symptoms adjustment
treatment for maintenance agitation Choice of dose involvement in Risk assessment Co-morbidities and
phase Harm prevention Family information and preventing suicide of drug co-medications
Family involvement in Recourse to involvement Identification of other interactions Risk-benefit assessment of
treatment choice parenteral treatment Psychosocial risk factors for suicide Management of benzodiazepine treatment
Assessment of metabolic Switch to interventions Diagnosis of co- drug dependence
risk factors maintenance therapy morbid mood
Psychosocial interventions disorders
Treatment of co-
morbid mood
disorders

Pharmacological Atypical antipsychotics
treatment without titration
Solutions or rapidly
dissolving forms
CNS Drugs 2009; 23 (3)
Oral treatment Atypical antipsychotics Clozapine Antipsychotics Atypical antipsychotics
preferred but Low metabolic risk profile Antidepressants with low risk of with proven efficacy in elderly
intramuscular interaction with patients
administration could drugs of abuse or In elderly patients with
be considered alcohol impaired hepatic function,
Antipsychotics with drugs eliminated principally
sedative effects by the kidney should be
preferred

In patients with impaired

renal function, drugs

Thomas et al.
eliminated principally by
hepatic metabolism should
be preferred
a For example, catatonia, co-morbidity, drug intoxication or drug withdrawal.
Management of Acute Psychosis
prevent relapse. Many patients have had previous
unsatisfactory experiences with antipsychotics
that produce extrapyramidal adverse effects, such
as dystonia, and will be unwilling to take the
same medication again. Use of an atypical anti-
psychotic should be proposed to such patients
with the reassurance that these drugs produce
fewer extrapyramidal symptoms than typical
agents. However, it should be borne in mind that
the risk of extrapyramidal symptoms is not zero
and will vary between atypical antipsychotics,
and that it is higher with high doses of risperidone
(>6 mg).[16,17] It is also important to take into
account other adverse effects that will influence
the acceptability of treatment, such as weight
gain, sexual dysfunction, metabolic problems and
symptomatic hyperprolactinaemia. Again, the
propensity of individual atypical antipsychotics
to produce such adverse effects varies. A suc-
cessful experience with an atypical antipsychotic
at this stage will help cement trust between
the patient and the physician and thus increase
the chances of establishing an effective ther-
apeutic alliance. If the patient has responded
successfully to a specific antipsychotic during a
previous relapse, and found the treatment ac-
ceptable, this drug should be considered for the
current episode.
A detailed medical history should be taken, an
ECG performed and a serum sample taken for
haematological and biochemical measurements,
notably of blood glucose, transaminases and li-
pids. Some atypical antipsychotics, notably clo-
zapine, olanzapine and zotepine, also carry the
risk of hyperglycaemia and development of dia-
betes mellitus.[18] In patients with metabolic risk
factors, an antipsychotic with a low propensity
for inducing weight gain, dyslipidaemia or dys-
glycaemia should be preferred, such as amisul-
pride, aripiprazole or ziprasidone,[19] since these
can be continued safely into the maintenance
phase. If drugs with a high metabolic impact are
used in the short term, it may be necessary to
switch to another drug for the maintenance
phase, with an associated risk of loss of symptom
control or of treatment adherence. Ziprasidone
and sertindole are contraindicated in patients
with cardiac rhythm disorders.[20-22] Use of a
ª 2009 Adis Data Information BV. All rights reserved.
197
sedative antipsychotic such as olanzapine or
quetiapine may be useful in the early stages of
treatment, but sedation is not always desirable
later on in treatment.[23] The incidence, intensity
or troublesomeness of somnolence produced
by these medications typically declines over
time,[24,25] although it should be recognized that
some patients may need a medication switch
during the maintenance phase because of seda-
tion. In most cases, it should be possible to con-
trol agitation and anxiety sufficiently with a
benzodiazepine without the need for a sedative
antipsychotic. However, the risk of developing
dependency on benzodiazepines if treatment is
prolonged should be taken into account when
choosing between this strategy and the use of a
sedative antipsychotic. In all cases, benzodiaze-
pines should be given for the minimum period
necessary. A comparison between the different
atypical antipsychotics is presented in table II.
Once the most suitable antipsychotic has been
identified, treatment should be started using the
most effective dose from the outset. For certain
atypical antipsychotics, such as risperidone[26]
and quetiapine,[27] incremental dose titration is
recommended, and this may not be appropriate
when rapid symptom control is required. Data
from positron emission tomography studies have
demonstrated that treatment regimens that re-
quire incremental dose titration do not achieve
full occupation of central dopamine receptors
during the first days of treatment.[28] Since there is
a critical threshold of dopamine receptor occu-
pancy for achieving the desired antipsychotic ef-
fect,[29,30] maximal antipsychotic effect may thus
be delayed when using treatments that require
gradual dose titration. In such cases, atypical
antipsychotics that can be used from the first
day at their recommended maintenance dose,
such as amisulpride or aripiprazole, may thus be
preferred. If treatment compliance is an issue,
solutions or rapidly dissolving forms are available
for certain antipsychotics. In general, oral admin-
istration of antipsychotics is recommended over
parenteral administration, since it requires co-
operation by the patient in taking medication and
is thus a first step towards building a therapeutic
alliance.[2,31]
CNS Drugs 2009; 23 (3)
198 Thomas et al.

Table II. Properties of atypical antipsychotics influencing choice of treatment in the initial phase. Data were taken from the relevant
European or US summaries of product characteristics
Drug Need for Drug Metabolic Sedative Other tolerability issues Short acting Solution
titration interaction impact effect IM form form
potential
Amisulpride No Low Low Low Elevated prolactin levels No Yes
Aripiprazole No Low Low Low Agitation Yes Yes
Clozapine Yes High High High Agranulocytosis, prolonged QTc No No
interval, orthostatic hypotension,
weight gain
Olanzapine In at-risk High High High Weight gain Yes Yes
patients
Quetiapine Yes Moderate Moderate High Weight gain No No
Risperidone Yes Moderate Moderate Low Elevated prolactin levels, weight gain No Yes
Sertindole Yes Lowa Low Low Prolonged QTc interval No Yes
Ziprasidone In at-risk Low Low Low Prolonged QTc interval Yes No
patients
Zotepine Yes High High Moderate Orthostatic hypotension, weight gain No Yes
a A specific issue is aggravation of cardiovascular risk (QT prolongation) when sertindole is used in combination with drugs that inhibit
its metabolism.
IM = intramuscular; QTc = corrected QT.

4.2 The First 4 Weeks Qualitatively similar findings were reported in a

The objectives in medium-term management
are to consolidate the therapeutic alliance and
ensure a smooth transition to the maintenance
phase with a treatment regimen that provides
optimal symptom control and quality of life with
minimal risk of adverse effects. Patients and fam-
ilies need to be fully informed about the po-
tential adverse effects of antipsychotic drug
treatment and provided with advice about how
these can be avoided or handled. Possible psy-
chosocial interventions and social rehabilitation
during the maintenance phase can be considered
and discussed with the patient and family, and
the necessary arrangements made for outpatient
facilities or social services.
Adverse effects, particularly extrapyramidal
symptoms, are a major determinant of long-
time treatment adherence and thus of the risk of
relapse.[32] A number of long-term studies have
provided evidence that atypical antipsychotics
provide superior relapse control to haloper-
idol.[33,34] For example, Csernansky et al.[35] repor-
ted a nearly 2-fold higher risk of relapse in
patients with schizophrenia treated with haloper-
idol compared with those receiving risperidone.
subsequent study in patients with first-episode
disease.[36] However, the CATIE (Clinical Anti-
psychotic Trials of Intervention Effectiveness)
trial,[37] performed in naturalistic care conditions,
did not provide any evidence for better treatment
retention in patients receiving a first-generation
antipsychotic (perphenazine) rather than an aty-
pical antipsychotic. In any case, treatment ac-
ceptability should be monitored carefully.
Psychopathology needs to be monitored closely
throughout the 4-week period. In patients with
persistent psychotic symptoms, the appropriate-
ness of the dose and duration of treatment should
first be assessed and adjusted if necessary to ensure
satisfactory treatment control. If the dose was
adequate, then it is important to evaluate the
adherence of the patient to medication. In cases
of non-response, blood concentrations of anti-
psychotics can sometimes be monitored to de-
termine whether adequate plasma concentrations
of drug are present.[38] This may be most useful
with amisulpride, olanzapine and quetiapine, for
which there is some evidence for a relationship
between plasma concentrations and antipsychotic
effects.[39-41] In contrast, no such relationship ex-
ists for a number of conventional antipsychotics,

ª 2009 Adis Data Information BV. All rights reserved. CNS Drugs 2009; 23 (3)
Management of Acute Psychosis
and in the case of risperidone the relationship is
paradoxical.[42,43] Monitoring may be helpful for
identifying ultrarapid metabolizers and detecting
potential drug-drug interactions leading to induc-
tion of hepatic enzymes. In cases of emergence of
other psychiatric symptoms, for example, depres-
sion, these should be treated. Certain atypical anti-
psychotics have been demonstrated to be effective
against depressive symptoms in schizophrenia,
including amisulpride,[44,45] aripiprazole[46] olan-
zapine,[47] quetiapine[48] and risperidone.[49] During
this period, benzodiazepines should be discon-
tinued, or the dose reduced as much as possible
if discontinuation is not possible without re-
emergence of agitation. Any hypnosedative medi-
cation should also be stopped.
As well as control over psychotic symptoms, it
is important to ensure that the treatment is well
tolerated. An ECG should be performed. Weight,
body mass index and waist circumference should
be monitored and blood samples taken for
haematology and measurement of transaminases,
blood lipids and glycaemia. If significant anom-
alies are detected, the patient should be switched
to another antipsychotic drug.
5. Highly Agitated Patients
Around 10–15% of patients are admitted in a
highly agitated state or with significant psychotic
anxiety and are considered to be at risk of harm
to self or others.[50-56] These patients require
hospitalization, in a closed ward if necessary. In
such patients, it is important to assess the nature
of the agitation. In particular, physicians should
consider delirium as a potential differential
diagnosis in psychotic patients who are agitated.
If agitation appears to be primarily delusional,
it should be recognized that it may be secondary
to psychotic symptoms and unlikely to resolve
before these symptoms are successfully treated.
Undirected agitation may indicate a delirium
resulting from drug intoxication or withdrawal,
brain damage or other co-morbid medical con-
ditions. This needs to be assessed, identified and
promptly managed, if necessary, once the state of
the patient permits.
ª 2009 Adis Data Information BV. All rights reserved.
199
5.1 The First 4 Days
In highly agitated patients, cooperation of the
patient in the treatment plan is not feasible and
rapid control of agitation is the immediate treat-
ment goal. This is important both for the psy-
chiatric well-being of the patient and to prevent
harm to the patient or others. Since these patients
are unlikely to be cooperative, physicians should
make every effort to obtain as much collateral
information as possible on the patient’s history
and clinical state from the family or hospital re-
cords. An antipsychotic should be chosen and
administered by a route and at a dose to ensure
rapid symptom relief and safety. The physician
will generally not have the time or the informa-
tion to make an informed choice on the most
suitable antipsychotic for a given patient and will
have to make a decision based on the overall ef-
ficacy and safety of the drug, as well as on the
psychopathological profile of the patient. An
antipsychotic with sedative properties such as
olanzapine or quetiapine may often be suitable in
such patients. Although oral treatment is the
preferred route of administration, as it requires
some degree of patient adherence and is less
coercive, in many cases this may be rejected by
the patient. In such cases, intramuscular admin-
istration should be considered. Intramuscular
injectable forms are available for several con-
ventional antipsychotics and for the atypical
antipsychotics olanzapine, ziprasidone and ari-
piprazole. These formulations offer the ad-
vantages of guaranteeing effective control over
psychotic symptoms, thus calming and reassuring
the patient and, from the physician’s perspective,
facilitating overall management of the patient.
On the other hand, injectable formulations pre-
sent certain disadvantages. For example, use of
intramuscular olanzapine[57] has been associated
with transient hypotension and bradycardia. Use
of intramuscular forms of certain conventional
antipsychotics is associated with significant neu-
rological adverse effects, which may make the
patient distrustful of treatment in general and
thus compromise adherence during the sub-
sequent consolidation and maintenance phases of
the treatment strategy.[58]
CNS Drugs 2009; 23 (3)
200
Table III. Recommended dose ranges for benzodiazepines for the treatment of agitation in patients with schizophrenia. Data were taken from
the relevant European or US summaries of product characteristics (SPC)
Drug Standard treatment (mg)
Alprazolam 4 Not indicated in SPC
Diazepam 15–20
Lorazepam 2–6
Benzodiazepines, in particular lorazepam, can
also be administered orally or intramuscularly.
Higher doses may be required compared with the
standard care paradigm (table III). In patients
who are particularly aggressive or violent, a
sedative antipsychotic such as pipamperone or
cyamemazine, or intramuscular olanzapine or
zuclopenthixol, may be preferred.
5.2 The First 4 Weeks
A therapeutic alliance can only be established
once the patient is no longer agitated and is re-
ceptive and cooperative. Establishing the ther-
apeutic alliance is the major goal for this period,
with the same objectives as in the standard
treatment paradigm. Selection of the most ap-
propriate antipsychotic for use in the main-
tenance phase needs to be made on the basis of
safety and previous patient experience. The
treatment chosen should be tailored to the needs
of the individual patient with respect to the
specific efficacy and tolerability profiles of indi-
vidual atypical antipsychotics, their potentially
beneficial effects on negative, cognitive and af-
fective symptoms, and their potential for adverse
effects such as hyperprolactinaemia, weight gain,
metabolic problems or sexual dysfunction. This
may well involve a change in medication from
that used at admission; the new treatment also
needs to be initiated, its tolerability assessed and
the dose adjusted adequately before the patient is
discharged. In patients with antecedents of poor
compliance to maintenance therapy or who
are at risk of being violent, use of a depot anti-
psychotic preparation may be considered. The
only atypical antipsychotic available in a depot
preparation currently is risperidone, although
such formulations are available for several
classical antipsychotics. In patients in whom
ª 2009 Adis Data Information BV. All rights reserved.
Thomas et al.
Highly agitated patients (mg) Elderly patients (mg)
Initially 0.125, may be increased gradually
20–40 Not indicated in SPC
Not indicated in SPC 0.5–3
aggressiveness is poorly controlled by the initial
antipsychotic treatment, adjunctive treatment
with mood stabilizers such as valproate may be
considered.[59]
6. First-Episode Psychosis
Patients presenting with their first psychotic
episode need to be investigated with particular
care so that the most appropriate long-term
treatment that will have the greatest success in
preventing future relapses can be instigated. With
appropriate initial treatment, a minority of
patients may never have another episode of acute
psychosis, although most (>80%) will have a
relapsing course.[60]
6.1 The First 4 Days
A comprehensive diagnostic work-up should
evaluate somatic and psychiatric co-morbidity,
as well as antecedents of drug abuse. The differ-
ential diagnoses of secondary psychosis, drug-
induced psychosis, delusional disorders and
depression with psychotic symptoms, or psycho-
tic mania need to be carefully ruled out.
Wherever possible, an atypical antipsychotic
should be used. Conventional antipsychotics
should be avoided because their adverse effects,
especially extrapyramidal symptoms, are an im-
portant determinant of long-term adherence to
treatment.[61] For example, Schooler et al.[36] re-
ported that the rate of relapse was significantly
lower and the time to first relapse significantly
longer in first-episode patients treated with ris-
peridone compared with those treated with
haloperidol. There is also some evidence from
randomized comparative studies that atypical
antipsychotics may have beneficial effects on
cognitive symptoms in first-episode patients,
CNS Drugs 2009; 23 (3)
Management of Acute Psychosis
and that these effects are superior to those ob-
served with first-generation antipsychotics.[62-67]
There is now a sufficiently large range of atypical
antipsychotics available to mean it should be
possible to find an effective treatment for all pa-
tients. Several meta-analyses of randomized
clinical trials have concluded that the overall
antipsychotic efficacy of these drugs is broadly
similar.[68-72] Several studies comparing first-
generation with atypical antipsychotics have
failed to demonstrate relevant efficacy differences
between medications, but have confirmed the
high susceptibility of first-episode patients to ad-
verse effects with first-generation drugs.[62,73-77]
The CAFÉ (Comparison of Atypicals for First-
Episode Psychosis) study directly compared
olanzapine, quetiapine and risperidone in first-
episode patients and found all drugs to be essen-
tially similar in terms of long-term (1-year)
adherence, control of psychotic symptoms,
response rates and tolerability, although weight
gain and other metabolic disturbances were
greatest for olanzapine and least for risper-
idone.[78] The EUFEST (European First Episode
Schizophrenia Trial) observational study, which
compared the effectiveness and tolerability of
four atypical antipsychotics (amisulpride, que-
tiapine, risperidone and ziprasidone) in first-
episode schizophrenia, has recently been
reported.[79] This study found that all atypical
antipsychotics evaluated in this study were asso-
ciated with significantly lower rates of any-cause
discontinuation (between 33% for olanzapine
and 53% for quetiapine) than haloperidol (72%).
However, the extent of symptom control in pa-
tients remaining on treatment was comparable
for all antipsychotic drugs tested.
Nevertheless, it should be recognized that
individual patients may respond better to one
atypical antipsychotic than another, although the
determinants of individual patient responses
remain poorly characterized. Patients presenting
with their first psychotic episode appear to be
more sensitive both to the antipsychotic effects of
treatment and also to its adverse effects.[80] For
this reason, a lower initial dose of antipsychotic
than that used in psychotic relapse is generally
effective in first-episode psychosis (table IV),
ª 2009 Adis Data Information BV. All rights reserved.
201
although results from the CAFÉ study indicate
that quetiapine may be an exception to this gen-
eral rule.[78] Clozapine has a limited role in first-
episode schizophrenia because its potentially
serious haematological adverse effects restrict its
use to treatment-resistant schizophrenia or to pa-
tients in whom the risk of suicide is high. Sertin-
dole is also not indicated as first-line treatment
for first-episode patients because of its cardiac
adverse effects (prolongation of the corrected QT
interval).[22]
The antipsychotic medication initiated at the
first episode should be considered as a potentially
lifelong treatment for individuals who are gen-
erally very young adults. For this reason, long-
term safety issues are important to consider,
particularly the metabolic adverse effects asso-
ciated with certain atypical antipsychotics and
the risk of early development of diabetes. Atypi-
cal antipsychotics also differ widely in cost, and
this may be an issue in certain countries.
Communication with the patient and family or
entourage, and provision of appropriate in-
formation and education need to be initiated
as soon as possible. This episode is likely to be
the family’s first close experience with schizo-
phrenia, and family members need to under-
stand the implications of the diagnosis as well
as being reassured as to the possibility of suc-
cessful treatment. A clear awareness by family
members of the issues and their involvement in
the treatment plan will help reduce subsequent
stigmatization when the patient returns to the
community.
6.2 The First 4 Weeks
During this period, treatment needs to be op-
timized and a long-term care plan elaborated. As
indicated above, individual patients may respond
more or less well to individual drugs. In cases of
suboptimal response to the drug initially used or
emergence of troublesome adverse effects, time
needs to be taken to change the treatment if
necessary until a drug and dose are identified that
provide effective symptom control and accept-
able tolerability. It is essential to ensure that pa-
tients and family understand the importance of
CNS Drugs 2009; 23 (3)
202 Thomas et al.

Table IV. Recommended dose ranges for atypical antipsychotics for initial treatment of acute psychotic episodes in patients with schizo-
phrenia. Data were taken from the relevant European or US summaries of product characteristics (SPC), except for the first-episode data
which were obtained from relevant clinical trials
Drug Standard treatment (mg) First episode psychosis (mg) Elderly patients (mg)
Amisulpride 800 600–800a 200–400
Aripiprazole 10–15 15[81] No dose adjustment required
Clozapine Initially 25, adjusted to NA Caution
300–450
Olanzapine Initial: 5–10 5–10[81] Initial: 5
Target dose: 10
Quetiapine Initial: 50 From 50 at day 1 to 400 at day 5[81] Lower doses
Target dose: 300–400
Efficacy dose: 150–750
Risperidone Initial: 2 2–4[81] Initial: 1
Target dose: 6
Efficacy dose: 4–8
Sertindole Initial: 4 NA No data, slower titration suggested
Target dose: 12–20
Ziprasidone Initial: 40 40[81] Lower dose, slower titration
Adjust to a maximum of 160
Efficacy dose: 20–100
Zotepine Initial: 75 Median of 250[81] 50–150
Target dose: 75–300
a Product SPC.
NA = not applicable, as only recommended as second-line therapy.

treatment adherence, that potential issues related
to adherence are investigated and that families
are prepared for dealing with relapses. Monitor-
ing for potential treatment adverse effects needs
to be initiated. As some atypical antipsychotics
carry a high risk of metabolic adverse effects,
monitoring and management guidelines have
been developed, for example by the American
Diabetes Association[18] and Wetterling,[82] to
reduce the risk of developing diabetes. In addi-
tion, patients should be informed about lifestyle
measures that may help prevent the emergence of
metabolic adverse effects.
As well as medication, the long-term care
plan needs to take into consideration psychoso-
cial interventions that will help the patient cope
with psychotic symptoms, measures to main-
tain or improve social integration, and access
to self-help groups to avoid stigmatization. It is
also important to discuss lifestyle issues with
patients and their families, emphasizing the ben-
efits of exercise, a healthy diet and good sleep
hygiene.
7. Patients at High Risk of Suicide
Patients with schizophrenia have a much
higher rate of suicide than individuals in the
general community, with psychosis being a major
cause of suicide in young adults. In a recent meta-
analysis, the lifetime risk of suicide following
onset of schizophrenia was estimated as 5.6%.[83]
In patients with antecedents of suicide attempts
or strong suicidal ideation, physicians should be
particularly vigilant as to the risk of suicide or
self-harm during the acute psychotic phase.
These patients should always be hospitalized,
either in a closed ward or in an open ward if
round-the-clock observation is possible.
In addition, several factors have been identi-
fied that are associated with a high suicide risk in
patients with schizophrenia. These include co-
morbid or previous depression, aggressiveness or
agitation, substance abuse, fear of mental dis-
integration, previous suicide attempts, social iso-
lation, recent bereavement and poor adherence to
treatment.[84-87] In patients presenting with such

ª 2009 Adis Data Information BV. All rights reserved. CNS Drugs 2009; 23 (3)
Management of Acute Psychosis
features, suicide risk and suicidal ideation should
be carefully evaluated, and the patients mon-
itored closely.[86]
7.1 The First 4 Days
While psychotic symptoms are still manifest, it
is useful to try and evaluate the contribution of
hallucinations to suicidal ideation. If this is sig-
nificant, then it would be useful to consider be-
havioural or psychosocial interventions during
the maintenance treatment phase that would help
the patient cope better with hallucinations during
future relapses. Personal and familial antecedents
of suicidality should be investigated and taken
into account when assessing suicide risk and
planning follow-up in the community. Careful
diagnostic evaluation may reveal the presence of
bipolar disorder, which should be treated with
mood stabilizers. During the first few days fol-
lowing admission, these patients should be kept
under close observation at all times.
With respect to the choice of antipsychotic
treatment, clozapine has been shown to reduce
suicidal ideation and suicide attempts in several
studies[88] and is superior to some other atypical
antipsychotics in this respect.[89] However, the
benefits of clozapine in terms of suicide risk need
to be carefully balanced against the risk of
potentially serious haematological or cardio-
vascular adverse effects. Otherwise, use of an
antipsychotic with strong acute sedative effects,
such as high dose olanzapine or quetiapine, or
short-term combination with a low-potency
sedative antipsychotic, could be considered.
7.2 The First 4 Weeks
The responsiveness of affective symptoms and
suicidal ideation to antipsychotic treatment
should be carefully monitored. Suicidal ideation
may be driven either by depressive symptoms or
by psychotic symptoms. Distress in reaction to
hallucinations and delusions is a key factor asso-
ciated with suicidal ideation in individuals with
psychotic relapse.[90] In susceptible individuals,
suicidal behaviour may also occur in response to
auditory hallucinations instructing the patient
how to act.[85,91,92] If depressive symptoms
ª 2009 Adis Data Information BV. All rights reserved.
203
predominate or persist, adjunctive therapy with
antidepressant drugs may be useful. An anti-
depressant with a low potential for clinically re-
levant drug interactions with antipsychotics and
benzodiazepines and with an optimal adverse
effect profile should be chosen; in particular,
selective serotonin reuptake inhibitors should
be considered in preference to tricyclic anti-
depressants. A switch to an antipsychotic with
effects on depressive symptoms, such as amisul-
pride or olanzapine, may also be considered.
It should be recognized that the risk of suicide
is high not only during the acute episode and
hospitalization but also during the first weeks
following discharge. This necessitates careful
evaluation of patients before they are discharged
into the community. If suicidal ideation persists,
a switch to clozapine could be made. Psychoso-
cial interventions following discharge from hos-
pital may be considered in order to reduce the
suicide risk over the long term.[86]
8. Patients Presenting with Drug
Intoxication and Withdrawal
Use of alcohol, tobacco and illicit drugs is high
in patients with schizophrenia, as is the degree of
co-morbid drug and alcohol dependence.[93-95]
Patients experiencing an acute psychotic epi-
sode may well be consuming large quantities
of psychoactive drugs, and drug intoxication or
withdrawal is a common primary cause of
presentation of acutely psychotic patients to
psychiatric services. These patients present spe-
cific challenges, as they are more likely to respond
less well to antipsychotic medication,[96] to re-
quire longer hospitalization,[97] to present an
elevated suicide risk[87] and to be poorly adherent
to treatment.[98] Such patients are best managed
on an inpatient basis.
8.1 The First 4 Days
At presentation, symptoms of drug intoxica-
tion or withdrawal are likely to be confounded by
psychotic symptoms, and the two need to be
carefully distinguished and treated appropriately.
The most conservative approach is to ensure all
CNS Drugs 2009; 23 (3)
204
substance use has stopped and wait for the drug-
related symptoms to disappear whilst controlling
psychotic agitation with a benzodiazepine. Benzo-
diazepines will also be beneficial in attenuating
symptoms of withdrawal from alcohol or other
drugs. Blood pressure and heart rate should be
monitored regularly because these may become
labile during withdrawal from psychostimulants
or alcohol. Any form of agitation is considered
to be a risk factor for neuroleptic malignant
syndrome.[99] In particular, this is a risk to be
considered with all antipsychotics in patients
experiencing drug withdrawal,[100] and anti-
psychotic treatment is best initiated once with-
drawal symptoms have abated.
When antipsychotic treatment is initiated, the
drug chosen should have a low risk of interaction
with drugs of abuse or alcohol. From a pharma-
codynamic point of view, this means choosing a
drug with a selective pharmacological profile that
has a restricted range of neurotransmitter and
receptor interactions, such as amisulpride or
ziprasidone. From a pharmacokinetic point of
view, drugs that are extensively metabolized by
the hepatic cytochrome P450 system, such as
olanzapine, or drugs that induce or inhibit these
enzymes, such as clozapine, should be avoided
wherever possible.
8.2 The First 4 Weeks
Before the patient returns to the community,
both the patient and his/her entourage need to
be educated on the risks associated with drug
dependence. A drug rehabilitation programme
should be initiated and effective treatment of
both addiction and schizophrenia integrated into
the long-term treatment plan.[101] The family or
entourage should be encouraged to be vigilant
with respect to adherence to this plan once the
patient leaves hospital. Treatment should involve
antipsychotic maintenance therapy, pharmaco-
therapy for the substance abuse if available and
appropriate, and motivational interviewing or psy-
chosocial interventions such as cognitive-beha-
vioural therapy.[101] Some atypical antipsychotics
may have a positive influence on substance use as
well as on psychotic symptoms.[102] Although no
ª 2009 Adis Data Information BV. All rights reserved.
Thomas et al.
prospective, randomized, controlled studies have
been performed, some evidence has been ob-
tained of a reduction in substance use in patients
with a dual diagnosis of schizophrenia and sub-
stance abuse treated with quetiapine,[103] risper-
idone,[104] ziprasidone,[104] amisulpride[105] and,
in particular, clozapine.[106-113]
9. Elderly Patients
Although the frequency and intensity of acute
psychotic episodes declines with age, the physi-
cian is nevertheless confronted with elderly pa-
tients presenting with acute psychosis in an
emergency psychiatric setting. In this context, it is
critical to distinguish accurately between schizo-
phrenia in the elderly and dementia with psy-
chosis. This has important consequences for the
prescription of antipsychotic medication in these
patients, as the risk-benefit ratio for these drugs
may not be favourable in patients with dementia.
In the CATIE-Alzheimer’s Disease (CATIE-AD)
study comparing three atypical antipsychotics ver-
sus placebo in patients with Alzheimer’s disease,
no better effectiveness for these drugs compared
with placebo was demonstrated.[114] In addition,
an increase in mortality due to cerebrovascular
disease in elderly patients with dementia-related
psychosis treated with antipsychotics has been
reported, leading to the US FDA mandating
an explicit warning about this risk in the pre-
scribing information.[115] This warning was issued
following an analysis of the results of 17 placebo-
controlled trials conducted with aripiprazole,
olanzapine, quetiapine or risperidone in elderly
demented patients with behavioural disorders.
These studies demonstrated a 1.6- to 1.7-fold in-
crease in mortality compared with patients receiv-
ing placebo, mostly due to cardiovascular events
or infections. At present, such risks have not been
identified in patients with schizophrenia, but it
should be noted that the large majority of ran-
domized clinical trials in schizophrenia have
specifically excluded older patients.
In addition, elderly patients with schizo-
phrenia present particular issues for management,
especially with respect to safety. Co-morbidity is
frequent in this age group, and cardiovascular
CNS Drugs 2009; 23 (3)
Management of Acute Psychosis
and gastrointestinal function may be particularly
impaired in elderly patients with schizophrenia
as a result of many decades of intensive alcohol
and tobacco use. In addition, elderly patients
are likely to be taking other medications, in-
creasing the potential for drug interactions with
the antipsychotic prescribed.
Many elderly patients are likely to have been
treated with conventional antipsychotics for dec-
ades, and the treating physician may be reluctant
to change a treatment with which the patient has
grown familiar. Nonetheless, these patients show
an increased sensitivity to the extrapyramidal effects
of these drugs,[116,117] especially tardive dyskinesia,
and may thus benefit from a switch to an atypical
antipsychotic with fewer or less severe extra-
pyramidal adverse effects. The atypical anti-
psychotic for which there is most experience in
the elderly is risperidone, which has been shown
to be a useful treatment option for switching from
conventional antipsychotics in this patient group.[118]
Randomized risperidone-controlled studies per-
formed in the elderly have also demonstrated
comparable efficacy to risperidone in this patient
group for both amisulpride[119] and olanza-
pine.[120] There is also more limited evidence for
the utility of quetiapine in elderly patients.[121]
Although treatment adherence might be expected
to be higher with atypical antipsychotics because
of their superior neurological adverse effect pro-
files, adherence may be compromised by distrust
arising from the switching of a long-standing
treatment or as a result of cognitive impairment.
The physician needs to weigh up these factors for
each individual patient before deciding to switch.
In addition, many elderly patients may present
co-morbidities that may be aggravated by the
adverse effects of individual antipsychotic drugs,
such as congestive heart failure, cardiac rhythm
disorders or diabetes, and these need to be taken
into account carefully in the treatment choice.[122]
Whatever the choice of antipsychotic rescue
medication, the dose should be lower than in
young adults because of the increased risk of ex-
trapyramidal adverse effects with conventional
agents and the cardiovascular adverse effects of
all drugs (table IV). In addition, the volume of
distribution of many lipophilic drugs is increased
ª 2009 Adis Data Information BV. All rights reserved.
205
and their rate of elimination decreased as a result
of age-related changes in hepatic and renal func-
tion, and in body fat and fluid distribution. These
pharmacokinetic changes also render necessary
the use of a lower dose. In elderly patients with
impaired hepatic function, a drug eliminated prin-
cipally by the kidney, such as amisulpride or ris-
peridone, should be used in preference to a drug
principally eliminated by hepatic metabolism,
such as olanzapine. Amisulpride is of particular
interest in the elderly since it is not metabolized to
any great extent[123] and thus can be used safely in
patients with impaired hepatic function and those
taking other medications that induce or inhibit
drug-metabolizing enzymes. In addition, amisul-
pride does not interfere with the metabolism of
other drugs.[124] In patients with impaired renal
function, on the other hand, olanzapine is more
suitable than amisulpride or risperidone.
Antipsychotic drugs with prominent anti-
muscarinic properties, such as clozapine and
olanzapine, should be used with caution in pa-
tients with prostate disease or glaucoma, as these
conditions can be aggravated by anticholinergic
drugs. In addition, antipsychotics with strong
sedative properties may increase the risk of falls
and mental confusion, and the doses of such
drugs should be minimized.[23] Similarly, drugs
that may cause orthostatic hypotension should be
used sparingly. As discussed above, treatment
with atypical antipsychotics is associated with an
increased risk of stroke in elderly patients with
dementia, although such an association has not
been identified to date in elderly patients with
schizophrenia. A hypothetical risk cannot, how-
ever, be excluded and patients with other risk
factors for stroke should be treated with caution;
in particular, hypertension should be controlled
and blood pressure monitored regularly in elderly
patients receiving antipsychotic medication.
Practice guidelines for the treatment of
schizophrenia in the elderly published by the
American Psychiatric Association recommend
the use of an atypical antipsychotic administered
at a dose one-half or lower than that used in
younger patients.[1] Similar recommendations
have since been put forward by the World Fed-
eration of Societies of Biological Psychiatry.[8]
CNS Drugs 2009; 23 (3)
206
Benzodiazepines must also be used with cau-
tion in the elderly, as sensitivity to these drugs
increases with age. The sedative effects of ben-
zodiazepines increase the risk of falls,[125] and
thus the risk of fracture, particularly in subjects
with osteoporosis. These sedative effects, as well
as effects of benzodiazepines on memory, may
cause confusion if the drugs are used at too high a
dose. This will also compromise the task of
gaining the patient’s confidence and adherence to
a treatment plan. It is important that the patient
remains a lucid partner in the therapeutic alli-
ance. Finally, high doses of benzodiazepines
can cause paradoxical disinhibition, which may
aggravate, rather than relieve, anxiety and agita-
tion. The dose of benzodiazepines should there-
fore be reduced in elderly patients compared with
that proposed for younger patients (table III).
10. Special Issues Related to Gender
There are a number of gender-specific issues
relating to the choice of antipsychotic for the
maintenance phase. Since the choice of main-
tenance antipsychotic treatment is made early,
and influences the choice of treatment in the
initial treatment phase, these issues should be
borne in mind during the initial treatment phase.
These issues relate to adverse effects of anti-
psychotics that may have different repercussions
in men and in women. For example, the signif-
icant weight gain associated with some atypical
antipsychotics may have a higher impact on self-
image and thus on quality of life in women than
in men. In men, certain antipsychotics have de-
leterious effects on sexual function,[126] with
around half of men treated with antipsychotics
reporting sexual adverse effects.[127,128] These are
considered among the most distressing adverse
effects of antipsychotics,[129] interfere strongly
with quality of life,[127] and are an important
reason for non-adherence to maintenance anti-
psychotic treatment.[128-136] Several atypical
antipsychotics can cause elevations of serum
prolactin level, notably risperidone and amisulpride,
although this is generally asymptomatic.[137,138]
Comparative randomized trials have indicated
that the risk of hyperprolactinaemia is higher
ª 2009 Adis Data Information BV. All rights reserved.
Thomas et al.
with risperidone than with amisulpride.[139] In-
creases in prolactin levels are generally reversible
after drug discontinuation. Hyperprolactinaemia
can sometimes lead to clinical manifestations
that are distressing to the patient.[140] Elevated
prolactin levels can cause dysmenorrhoea, ame-
norrhoea or anovulation as well as tender breasts
in women. In addition, hyperprolactinaemia
is a well characterized risk factor for osteopo-
rosis[140-144] and some, but not all, studies suggest
that hyperprolactinaemia may also be asso-
ciated with a higher risk of breast cancer.[145-148]
In men, rare cases of galactorrhoea have been
described in patients taking these drugs, although
male hyperprolactinaemia is associated with
gynaecomastia, decreased libido, erectile dys-
function and reduced sperm count.[149]
The second-generation antipsychotic drugs
are contraindicated in pregnancy. However,
discontinuation of antipsychotic drugs for a
9-month period during pregnancy carries an ele-
vated risk of psychotic relapse. Experience has
accrued over the years on the use of anti-
psychotics during pregnancy and the associated
risks. If women are to take antipsychotic medi-
cation during pregnancy, caution would advise
selection of a drug for which there is more ex-
perience compared with recently introduced treat-
ments. The metabolism of oral contraceptives
may be influenced by antipsychotic drugs that
inhibit or induce hepatic cytochrome P450 drug-
metabolizing enzymes, with a potential loss of
contraceptive control. It should be noted that this
has not been observed clinically, but remains a
hypothetical possibility. It is also inappropriate
for women taking highly sedative antipsychotic
drugs, or drugs with marked extrapyramidal ad-
verse effects, to breast feed. Most antipsychotics
are highly lipophilic and pass readily into breast
milk, and insufficient information is currently
available about the safety of antipsychotic drugs
and their impact on child development.
11. Conclusion
The initial management of patients presenting
with acute psychosis needs to be adapted to the
CNS Drugs 2009; 23 (3)
Management of Acute Psychosis
individual characteristics and needs of each pa-
tient. The core treatment consists of administra-
tion of benzodiazepines to control agitation and
of antipsychotics to control psychotic symptoms.
Oral medication is preferable to injectable forms
wherever possible, and atypical antipsychotics
are to be preferred over conventional agents. The
antipsychotic chosen during the initial period
is likely to have to be continued for many years,
and the long-term safety profile of the drug
should be taken into account when making this
choice, particularly in relation to extrapyramidal
adverse effects, metabolic complications and
quality of life. In addition to drug treatment, the
initial management of psychosis should aim to
build a therapeutic alliance with the patient and
to elaborate a long-term treatment plan in con-
cert with the patient and family. The long-term
goal should be to minimize the risk of psychotic
relapse through adequate treatment adherence.
The importance of tailored psychosocial inter-
ventions in maintaining social integration and in
reinforcing treatment adherence should not be
neglected.
Acknowledgements
No sources of funding were used to assist in the prepara-
tion of this review. Dr Thomas has received honoraria and
educational/research grants from Lilly, Janssen-Cilag, Bristol-
Myers Squibb and sanofi-aventis. Dr Alptekin has acted as a
consultant to Lundbeck, Janssen, Pfizer, Lilly, Sanovel,
sanofi-aventis, Eczacibasi-Zentiva, EGIS and Bristol-Myers
Squibb, and has received educational/research grants from
Lundbeck, Pfizer and Wyeth. Dr Gheorghe has received hon-
oraria from sanofi-aventis. Dr Olivares has acted as a consul-
tant to and/or received honoraria from Janssen-Cilag, Lilly,
AstraZeneca, sanofi-aventis, Lundbeck, Bristol-Myers Squibb
and GlaxoSmithKline. Dr Riedel has acted as a consultant to
and received honoraria from Otsuka Pharmaceuticals, Astra-
Zeneca, Pfizer and Janssen-Cilag; has received honoraria
from Lilly, Sanofi-Synthelabo and GlaxoSmithKline; and has
received educational/research grants from Otsuka Pharma-
ceuticals, Bristol-Myers Squibb, AstraZeneca, Pfizer, Lilly
and Sanofi-Synthelabo. Dr Mauri has no conflicts of interest
that are directly relevant to the content of this review.
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Correspondence: Prof. Pierre Thomas, Pôle de Psychiatrie,
Hopital M. Fontan, CHRU de Lille, Rue Veraeghe, 59037
Lille, Cedex, France.
E-mail: pthomas@chru-lille.fr
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