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Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment
Authors Section Editor Deputy Editor

T. Scott Stroup, MD, MPH Murray B Stein, MD, MPH Richard Hermann, MD
Stephen Marder, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2016. | This topic last updated: Jul 24, 2015.
INTRODUCTION Schizophrenia is a psychiatric disorder involving chronic or recurrent psychosis. It is

commonly associated with impairments in social and occupational functioning [1]. It is among the most
disabling and economically catastrophic medical disorders, ranked by the World Health Organization as one
of the top ten illnesses contributing to the global burden of disease [2].
Antipsychotic medications are first-line medication treatment for schizophrenia. They have been shown in
clinical trials to be effective in treating symptoms and behaviors associated with the disorder. Antipsychotic
medications have significant side effects; assessment and management of these adverse effects are an
important part of treatment. Evidence-based psychosocial interventions in conjunction with pharmacotherapy
can help patients achieve recovery.
This topic addresses the pharmacotherapy of schizophrenia in acute and maintenance phase treatment.
Discussed separately are the use of long-acting antipsychotics and management of side effects during
pharmacotherapy for schizophrenia; the epidemiology, pathogenesis, clinical manifestations, and diagnosis
of schizophrenia; psychosocial interventions for schizophrenia; and common comorbid presentations of
schizophrenia. (See "Pharmacotherapy for schizophrenia: Long-acting injectable antipsychotic drugs" and
"Pharmacotherapy for schizophrenia: Side effect management" and "Schizophrenia: Epidemiology and
pathogenesis" and "Schizophrenia: Clinical manifestations, course, assessment, and diagnosis" and
"Psychosocial interventions for schizophrenia" and "Anxiety in schizophrenia" and "Depression in
schizophrenia" and "Co-occurring schizophrenia and substance use disorder: Epidemiology, pathogenesis,
clinical manifestations, course, assessment and diagnosis" and "Guidelines for prescribing clozapine in
schizophrenia".)
ACUTE PHASE The focus of treatment in schizophrenia changes as individuals enter different phases of
the illness. An acute phase occurs when patients with a prior history of schizophrenia have a psychotic
relapse, or during the first episode of psychosis. At this time, the focus is on reducing the severity of
psychotic thoughts and behaviors. (See "Schizophrenia: Clinical manifestations, course, assessment, and
diagnosis", section on 'Clinical manifestations'.)
Pre-treatment assessment When feasible, patients who are started on an antipsychotic medication
should receive a baseline physical examination with a neurological exam. Particular attention should be
focused on factors that may be affected adversely by antipsychotic medication: (See "Pharmacotherapy for
schizophrenia: Side effect management".)
Body mass index (BMI)
Waist circumference
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Heart The
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Blood pressure
Signs of a movement disorder:
Extrapyramidal symptoms (EPS): akathisia, parkinsonism, dystonias
Tardive dyskinesia: abnormal movements of the face, peri-oral areas, tongue, extremities
When feasible, laboratory evaluations should be initiated before starting an antipsychotic. With the exception
of patients treated with clozapine, the antipsychotic can usually be started before the results of laboratory
tests are available.
CBC, electrolytes, fasting glucose, lipid profile, liver, renal and thyroid function tests
White blood cell (WBC) count with differential for patients treated with clozapine
ECG for patients with a cardiac history or those being treated with antipsychotics that may prolong the
QT interval such as clozapine, thioridazine, iloperidone, ziprasidone.
Drug efficacy Antipsychotic drugs are first-line treatment for schizophrenia. Randomized trials have
shown that antipsychotics reduce positive symptoms of schizophrenia, such as hallucinations, delusions,
and suspiciousness, compared to placebo [3]. Antipsychotics eliminate or reduce these symptoms to a
tolerable level in about 70 percent of patients with schizophrenia [4]. (See "Schizophrenia: Clinical
manifestations, course, assessment, and diagnosis", section on 'Positive symptoms'.)
Neither antipsychotic medications nor other drugs have shown efficacy in treating negative symptoms in
schizophrenia, which include decreased expressiveness, apathy, flat affect, and a lack of energy. A
meta-analysis studied the efficacy of medication treatment for negative symptoms in 12,318 patients with
schizophrenia in 168 randomized trials [5]. Small statistically significant reductions in negative symptoms
were found for second-generation antipsychotics, antidepressants, glutamatergic agents, and combinations
of these medications, but not for first-generation antipsychotics and brain stimulation. None of the beneficial
effects for any of the medication strategies were considered to be of a clinically significant magnitude. (See
"Schizophrenia: Clinical manifestations, course, assessment, and diagnosis", section on 'Negative
symptoms'.)
With the exception of clozapine, careful systematic reviews and meta-analyses have not found convincing
evidence that any of the antipsychotics are more effective than any other for acute schizophrenia [6].
Clozapine is more effective for patients who do not respond fully to other antipsychotics, but due to
increased risk of agranulocytosis is reserved for those who do not respond well to or cannot tolerate other
antipsychotics. (See 'Treatment-resistant schizophrenia' below and "Treatment-resistant schizophrenia" and
"Guidelines for prescribing clozapine in schizophrenia".)
Antipsychotic selection There are important differences among the antipsychotics in areas other than
efficacy, including side effects and available formulations (table 1 and table 2). As a result, the selection of
an antipsychotic is often based on these considerations. The selection may vary for select populations
including individuals in a first psychotic episode, individuals who are only partial responders to
antipsychotics, patients who are agitated, and individuals who are sensitive to particular side effects such as
weight gain, EPS, or sedation. (See 'Initial management of refractory symptoms' below and 'Managing first
episodes' below and 'Management of agitation' below and "Pharmacotherapy for schizophrenia: Side effect
management".)
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categories monly grouped into two
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categories, with second-generation (or atypical) applied to clozapine and all antipsychotics first marketed
after clozapine was approved in 1989, and first-generation applied to antipsychotics marketed previously.
Recent clinical research, however, has strongly suggested that the distinction between first- and second-
generation antipsychotics has questionable validity and is confusing [6]. The pharmacologic properties,
therapeutic effects, and adverse effects are not distinct between and are heterogeneous within the groups.
Nevertheless, the terms first- and second-generation antipsychotic are still in widespread use. A valid
distinction is that the newer (second-generation) antipsychotics tend to cause fewer extrapyramidal side
effects than the older ones, particularly at the high end of approved dosage ranges.
Administration The dose of most antipsychotic drugs should be titrated from an initial dose to the
therapeutic range as quickly as tolerated. Quetiapine, clozapine, and iloperidone need to be increased
gradually before reaching a therapeutic dose. The timeframe for titration differs for each drug and also
depends on the individual patients tolerance of the drugs tendency to cause sedation and hypotension. In
most cases, patients can reach a therapeutic level in five or six days with quetiapine and iloperidone, and
two to three weeks with clozapine. Suggested dosing and side effect profiles for each antipsychotic drug are
shown in tables (table 1 and table 2).
Because identifying the appropriate dose range can be difficult in the pre-marketing phases of drug
development, the antipsychotic doses listed (table 2) deviate somewhat from those approved by the US
Food and Drug Administration, reflecting more recent research findings or clinical experience. Examples
include:
Haloperidol is effective and most useful at doses drastically below the FDA-specified maximum of 100
mg/day. Optimal haloperidol dosages are usually below 10 mg/day and almost always below 20
mg/day.
Optimal dosages of risperidone are lower than the approved 16 mg/day; typically, a maximum dose for
risperidone is 6 to 8 mg/day.
Resolution of psychotic symptoms generally occurs over several days and may take as much as four to six
weeks. Clinicians should avoid the impulse to change the medication or dose prematurely. Once the dose
reaches the therapeutic range, the decision to increase the dose should follow at least several days of
treatment during which the individual shows little or no improvement. Higher dosing should be accompanied
by careful observation of the patient for side effects. If patients fail to show improvement on doses above the
usual therapeutic range, the dose should be reduced.
As an example, a patient treated with risperidone can be started on 2 mg administered as a single daily dose
or 1 mg twice a day. If this dose is well tolerated (ie, minimal sedation, hypotension, or akathisia) the dose
can be increased to 3 mg on the second day and 4 mg on the third day. Since 4 mg is in the therapeutic
range for most patients, the clinician may then choose to continue this dose for an additional two weeks
before considering an increase. If the patient shows only minimal or no improvement, the dose can be
increased up to 8 mg daily with careful monitoring for clinical response and side effects. Doses of
risperidone above 8 mg daily are associated with substantial risk of EPS.
Because of dose-related toxicities, antipsychotics should be used at the lowest dose that is effective for an
individual. The toxicities of antipsychotic drugs typically increase with higher doses while therapeutic effects
can reach a maximum. At high doses, the adverse effects of an antipsychotic may surpass the marginal
benefit of dosage increases. As a result, increasing the dose of antipsychotic for a patient who is already
experiencing significant EPS is unli Close
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Course of response When a patient with schizophrenia is administered an antipsychotic medication, the
initial response is often a side effect such as sedation, restlessness, or postural hypotension. It is important
to explain this to patients, or they may conclude that the medication is ineffective or worsening their
condition. Most patients who will improve on an antipsychotic show the most rapid improvement in the first
two weeks [10]. Although the rate of improvement may slow after two weeks, patients will often continue to
improve during subsequent weeks and months.
During the first weeks of treatment, patients may first experience a decrease in the severity of symptoms. As
a result, the impact of symptoms on patient behavior may be reduced [11]. Hallucinations or delusions may
be less frightening or the patient may find that they can distract themselves by focusing their attention
elsewhere [12]. Delusions that are based on misinterpretations from an earlier time may linger, whereas the
tendency to misinterpret new information may be reduced.
INITIAL MANAGEMENT OF REFRACTORY SYMPTOMS Patients should be observed on a stable dose

of an antipsychotic for two to six weeks before concluding the drug is ineffective. The duration of the trial will
vary depending on a number of factors:
Although patients improve most rapidly during the first two weeks, they may continue to improve for
several weeks or even months on a stable dose [10].
However, recent evidence suggests that if patients show only a minimal response to an antipsychotic
drug during the first two weeks, it is unlikely that the individual will have a robust response [13]. The
2009 Schizophrenia PORT recommends that trials last for two to six weeks. This timeframe will be
slightly longer for antipsychotics such as iloperidone and quetiapine, which require slow titration.
Dose adjustments In cases of nonresponse or partial response, the antipsychotic dose can be gradually
increased toward the high end of the recommended range (table 2).
Most careful studies of doses above the recommended range have not found higher doses to be more
effective than the maximal recommended dose [14,15]. If used, trials of higher doses should be time limited,
with reassessment planned within three months. Unless clear evidence of improvement is seen, high doses
should not be continued [16].
A dose reduction can be helpful in cases where side effects, such as akathisia, parkinsonism, sedation, or
insomnia have obscured the benefit of a higher antipsychotic dose, or have been mistaken for signs of
ineffective treatment, such as agitation or negative symptoms.
Changing to another antipsychotic Switching antipsychotics can be helpful when a poor response is
related to side effects. As an example, in the large US effectiveness study of antipsychotic treatment for
schizophrenia, the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE), patients who gained
weight during the first phase of antipsychotic treatment frequently lost weight when they were changed to
ziprasidone, an antipsychotic that is not associated with weight gain [17].
Switching antipsychotics is less clearly beneficial when the initial medication lacked effectiveness. Most
studies have shown that poor responders to one antipsychotic are likely to be poor responders to another
antipsychotic except when the second agent is clozapine. (See 'Treatment-resistant schizophrenia' below.)
As an example, an analysis of patients who were on olanzapine, quetiapine, or risperidone prior to the
CATIE trial showed that the patients on olanzapine or risperidone who were randomly assigned to continue
the same antipsychotic had better outcomes than patients who were randomly assigned to change
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antipsychotics
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Administration Two basic strategies for changing antipsychotics are [19,20]:
A standard cross-titration for a stable patient: Simultaneous taper of the current medication with
titration of the replacement drug in three to four steps over several days to several weeks.
For patients at higher risk of relapse, the current medication is maintained at its full dose as the new
medication is increased. Once the second drug has reached its target dose, the first medication may
be gradually decreased and discontinued. In most cases this change can be managed in one to two
weeks.
Discontinuation of antipsychotic medications is generally well tolerated, except for clozapine, for which both
cholinergic rebound and withdrawal-emergent movement disorders have been reported [21-23]. A slow taper
of clozapine over one to two weeks is recommended. Chlorpromazine and thioridazine can also cause
cholinergic rebound and should be reduced over a week or more.
Adding a second antipsychotic Clinicians often add a second antipsychotic when patients have a
suboptimal response to a single drug. Little empirical evidence supports this practice [24]. Although some
randomized trials indicated that augmentation of clozapine with another antipsychotic may have some
benefit, a meta-analysis of this practice found the supporting evidence to be weak [25].
TREATMENT-RESISTANT SCHIZOPHRENIA Patients with schizophrenia who respond inadequately to

an initial antipsychotic, dose adjustments, or a change in antipsychotics are classified as having treatment-
resistant schizophrenia. The efficacy of interventions for treatment-resistant schizophrenia, including
clozapine, is discussed separately. Guidelines for clozapine prescribing, dosing, monitoring, and side-effect
management are described separately. (See "Treatment-resistant schizophrenia" and "Guidelines for
prescribing clozapine in schizophrenia".)
CLOZAPINE FOR SUICIDALITY IN SCHIZOPHRENIA Clozapine has been shown in randomized trials
to reduce suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide
[26]. A patient with schizophrenia who has persistent suicidal ideation warranting clinician concern may
benefit from a trial of clozapine. Guidelines for clozapine prescribing, dosing, monitoring, and side-effect
management are described separately. Management of suicidal patients is described separately. (See
"Guidelines for prescribing clozapine in schizophrenia" and "Suicidal ideation and behavior in adults".)
MANAGEMENT OF AGITATION Clinical management of the acutely agitated patient with schizophrenia
is a common objective on inpatient units and other settings. Agitation can be defined as a state
characterized by motor restlessness, excitement, and mental tension.
Causes Treatment of agitation in patients with schizophrenia should be guided by the cause, which can
include extrapyramidal symptoms (EPS), substance use, or psychosis.
Extrapyramidal symptoms Akathisia can be difficult to distinguish from psychotic agitation when
patients are unable to describe the experience of restlessness [27]. Akathisia can be treated with a
benzodiazepine; eg, lorazepam can be started at 0.5 mg orally twice daily and incrementally increased to a
maximum of 6 to 10 mg/day.
Substance use Up to half of individuals with schizophrenia have a comorbid substance use disorder
[28]. Use of stimulants such as phencyclidine (PCP), methamphetamine, and cocaine can cause agitation,
as can withdrawal from alcohol or benzodiazepines. Agitation from substance use or withdrawal can be
diagnosed by a history, physical ex rapy for comorbid disorders' below
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manifestations, course, assessment and diagnosis".)
Psychosis Psychotic symptoms of schizophrenia, such as frightening delusions, suspiciousness, and

command hallucinations can cause patients to become agitated. The agitation associated with psychosis
can be treated with an antipsychotic or an antipsychotic combined with a benzodiazepine. The selection of a
drug and the route of administration depend on a number of considerations including the urgency of calming
the patient and the cooperativeness of the patient [29]. As noted below, the choice of an antipsychotic
depends on the formulation selected. It is important to note that the treatment goal is to induce a calmer
state, which can often be accomplished without inducing sedation.
Treatment Although antipsychotic medications can take days to weeks before having a robust
antipsychotic effect, they generally have a calming effect within minutes for agitated patients. The route of
administration influences time to onset, as described below (table 3). (See "First-generation antipsychotic
medications: Pharmacology, administration, and comparative side effects" and "Second-generation
antipsychotic medications: Pharmacology, administration, and side effects".)
Standard oral formulations: Although many clinicians tend to favor sedating antipsychotics for agitated
patients, non-sedating agents can also be effective for reducing agitation. Risperidone 1 to 2 mg or
olanzapine 5 to 10 mg will usually be effective in these circumstances.
Oral rapidly dissolving formulations: Oral rapidly dissolving formulations are available for risperidone,
olanzapine, asenapine, and aripiprazole. These formulations are helpful when a patient is willing to
take a pill by mouth, but either cannot or does not swallow it. Dosing for these formulations is the same
as for standard oral formulations, eg, risperidone 1 to 2 mg or olanzapine 5 to 10 mg.
Short-acting intramuscular (IM) injectable formulations (eg, haloperidol, olanzapine, aripiprazole, and
ziprasidone): Olanzapine 5 or 10 mg administered intramuscularly is a good choice under most
circumstances. IM haloperidol is effective but should be given with benztropine or diphenhydramine to
reduce the risk of severe EPS including dystonias.
A combination of haloperidol 5 mg, lorazepam 2 mg, and benztropine 1 mg given intramuscularly

can be effective to treat severe agitation in schizophrenia.
We advise against the use of IM chlorpromazine, which can induce severe postural hypotension.
Akathisia from any IM antipsychotic can contribute to agitation.
Injectable IM antipsychotics have two potential advantages over oral antipsychotics. First, they
can be administered safely to uncooperative individuals. Second, patients reach an effective
plasma concentration sooner than with oral formulations. For example, patients may experience a
calming effect within 10 to 30 minutes following IM administration. Calming effects may take 30 to
60 minutes following oral administration.
Although repeat administration of an oral or intramuscular antipsychotic is common when the prior dose
does not sufficiently reduce agitation, the overall antipsychotic dose should be limited, because these
medications can cause significant side effects such as hypotension, EPS, and sedation, particularly at high
doses over a brief period of time [10]. Maximum antipsychotic doses are shown in a table (table 3).
To limit the amount of antipsychotic used, most physicians either start with a combination of an antipsychotic
and benzodiazepine or use a benzodiazepine when patients fail to respond to one or two doses of an
antipsychotic for agitation. rally or 0.5 to Close
1 mg intramuscularly
for calming.
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MANAGING FIRST EPISODES Patients in a first psychotic episode tend to have higher response rates
than patients who have experienced multiple psychotic episodes. These individuals also respond to lower
antipsychotic doses [30]. At the same time, younger patients and first episode patients have a greater
vulnerability to side effects such as weight gain and extrapyramidal side effects (EPS) [31]. Since many first
episode patients are also reluctant to take an antipsychotic, it is important to minimize adverse effects.
The Schizophrenia Patient Outcomes Research Team (PORT) recommended treating first episodes with
antipsychotics other than clozapine or olanzapine. Both of these medications are associated with more
weight gain, insulin resistance and dyslipidemia than other antipsychotics [3]. In addition, clozapine can
cause agranulocytosis.
The Schizophrenia PORT recommended that first-episode patients receive antipsychotic doses in the lower
half of the recommended dose range [3]. As examples, a first-episode patient would be treated with 1 to 3
mg of risperidone or 10 mg of aripiprazole daily. An exception to this recommendation should be made for
quetiapine, which may require titration to 500 to 600 mg daily.
MAINTENANCE TREATMENT Patients with schizophrenia who have recovered from an acute psychotic
episode will usually reach a stable or maintenance phase in which psychotic symptoms are reasonably well
controlled. The goal of maintenance antipsychotic treatment of schizophrenia is to minimize symptoms and
functional impairments, avoid relapses, and promote recovery that allows self-determination, full integration
into society, and pursuit of personal goals.
Efficacy For patients with schizophrenia who have recovered from an acute psychotic episode, we
suggest that antipsychotic medication should be continued indefinitely, even for patients who have achieved
remission from a first psychotic episode. This suggestion is in accordance with the recommendation of the
Schizophrenia PORT [3]. The lowest effective dose that achieves therapeutic goals should be used. Patients
should participate in the clinical decision-making regarding the duration of antipsychotic drug treatment.
Multiple randomized trials have found that maintenance antipsychotic medication reduces the risk of relapse
over a period of up to two years. A meta-analysis of 6493 patients with schizophrenia in 65 randomized trials
of 7 to 12 months duration found that patients who continued on an antipsychotic experienced a lower
relapse rate compared to patients withdrawn from an antipsychotic and receiving placebo (27 versus 64
percent; number needed to treat to benefit = 3, 95% CI 23) [32]. Other studies of up to two years have
found similar results [33].
A seven-year follow-up assessment of patients randomly assigned to either a dose reduction strategy or to
maintenance antipsychotic treatment found results that conflict with the studies of up to two years. Two
reports that follow describe an intervention and follow-up assessment of patients who experienced a first
episode of psychosis and subsequently met criteria for remission prior to enrollment in the trial [34,35].
The initial trial randomly assigned 128 patients to continue maintenance treatment or to a dose
reduction strategy [34]. After two years, patients assigned to the dose reduction strategy had a higher
rate of relapse, without offsetting advantages, compared to patients continuing on maintenance
treatment.
A subsequent assessment at seven years follow-up included 103 of the 128 patients (81 percent) who
participated in the trial [35]. Patients who had originally been assigned to the dose reduction strategy
experienced a higher rate of recovery (ie, symptomatic and functional remission) compared to patients
originally assigned to mainten
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More studies of longer term outcomes of maintenance treatment versus dose reduction are needed before
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we would suggest an approach other than indefinite continuation of maintenance treatment for patients with
schizophrenia following an acute episode of psychosis.
As these trials demonstrate, some people with schizophrenia do well without continuous antipsychotic
treatment; however, they are not identifiable prospectively [36].
Other considerations regarding selection of antipsychotic medication for maintenance treatment mirror those
for pharmacotherapy during the acute phase. (See 'Drug efficacy' above.)
Medication adherence Long-acting injectable antipsychotics may be useful for patients with
schizophrenia who experience frequent relapses due to non-adherence to antipsychotic medications. They
also may be helpful for patients who will not take oral antipsychotics regularly. (See "Pharmacotherapy for
schizophrenia: Long-acting injectable antipsychotic drugs".)
Other strategies to promote better adherence to antipsychotics include simplifying medication regimens (eg,
fewer medications, fewer pills, fewer daily doses) and active engagement of patients in treatment planning
(ie, shared decision making).
Treatment of cognitive impairment Improving cognitive impairment has increasingly become an

objective of treatment for schizophrenia. Preliminary studies suggest that antipsychotic medication may
improve cognition when received early in the course of schizophrenia [37,38]. Studies of patients with
chronic schizophrenia have generally found less improvement in cognition during antipsychotic treatment
[38-41]. Trials of other medications (including n-methyl-d-aspartate (NMDA) glutamatergic receptor agonists,
glycine, D-serine, ampakine CX516, D-cycloserine, donepezil, rivastigmine, and galantamine) have failed to
show significant benefit [42-50].
Pharmacotherapy for comorbid disorders Depressive disorders and anxiety disorders can be
challenging to diagnose in patients with schizophrenia. A primary comorbid disorder needs to be
distinguished from symptoms of schizophrenia, antipsychotic drug side effects, and other clinical
presentations. Properly diagnosed, however, these syndromes can respond to antidepressant and anxiolytic
medications [51]. (See "Depression in schizophrenia" and "Anxiety in schizophrenia".)
Substance abuse and dependence occur at a high prevalence in schizophrenia [52]. The combination of a
severe mental illness and a substance use disorder (SUD), commonly described as dual diagnosis, is
associated with increased morbidity, poorer functioning, decreased adherence to medication, and higher
rates of relapse compared to either disorder individually [53]. Integrated treatment strategies for dual
diagnosis that include pharmacotherapy have been developed for individuals with schizophrenia and SUDs.
(See "Co-occurring schizophrenia and substance use disorder: Epidemiology, pathogenesis, clinical
manifestations, course, assessment and diagnosis".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics
and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5 th to 6th
grade reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer short,
easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who
want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail
these topics to your patients. (You can also locate patient education articles on a varietyClose
of subjects by
searching on patient info and the
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Basics topics (see "Patient information: Schizophrenia (The Basics)")
SUMMARY AND RECOMMENDATIONS
Patients treated with an antipsychotic for schizophrenia should be assessed prior to treatment if
possible and at regular intervals for: (See 'Pre-treatment assessment' above.)
Signs of a movement disorder including extrapyramidal symptoms and tardive dyskinesia
Symptoms of metabolic syndrome including measurements of body mass index, waist

circumference, hemoglobin A1c, serum lipids, and blood pressure
ECG for patients with a history of cardiac disease or when starting an antipsychotic that prolongs
the QT interval
We recommend antipsychotic medication as first-line medication treatment for acute and maintenance
phase treatment for schizophrenia (Grade 1A). (See 'Drug efficacy' above.)
For patients with schizophrenia who have recovered from an acute psychotic episode, we suggest that
antipsychotic medication should be continued indefinitely at the lowest effective dose that achieves
therapeutic goals (Grade 2C). This approach is suggested even for patients who have achieved
remission from a first psychotic episode. (See 'Maintenance treatment' above.)
The selection of which antipsychotic medication to use for an individual patient with schizophrenia
should be made based on patient clinical factors and the side effect profiles of antipsychotic drugs.
With the exception of clozapine for patients with refractory symptoms, there is not convincing evidence
to favor one antipsychotic over the others based on efficacy. (See 'Drug efficacy' above.)
Because olanzapine is associated with significant weight gain and metabolic adverse effects,
leading guidelines state that it should not be used as a first-line agent for first-episode patients,
but should be considered for patients who fail treatment with a first-line agent.
Other strategies for the patient with schizophrenia who has not adequately responded to an
antipsychotic drug include:
Changing to another antipsychotic has been shown to be an effective strategy for addressing side
effect problems but is not clearly associated with improved efficacy, with the exception of
clozapine. (See 'Changing to another antipsychotic' above.)
Clozapine. (See "Treatment-resistant schizophrenia", section on 'Clozapine' and "Guidelines for

prescribing clozapine in schizophrenia".)
Adding a second antipsychotic medication has not been proven efficacious in randomized trials.
For patients with psychotic symptoms that do not respond to two trials of antipsychotic
monotherapy, a trial of clozapine is strongly recommended before combining two antipsychotics.
(See 'Adding a second antipsychotic' above.)
Hospitalized patients with schizophrenia may require treatment for agitation. If agitation is associated
with psychotic symptoms of schizophrenia, it can be treated with a standard oral formulation, rapid
dissolving, or intramuscularly injected antipsychotic, depending on the level of patient participation.
Other causes of agitation should be ruled out, including akathisia and substance abuse or withdrawal.
(See 'Management of agitatio Close
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Long-acting injectable (LAI) antipsychotic medication may be useful for patients with schizophrenia
when non-adherence to oral antipsychotics leads to frequent relapse. LAI antipsychotics are
administered at two to four week intervals. As an example, fluphenazine decanoate can be
administered at a dose between 6.25 to 50 mg intramuscularly every two weeks. Extrapyramidal
symptoms can be prominent at higher doses. (See 'Medication adherence' above and
"Pharmacotherapy for schizophrenia: Long-acting injectable antipsychotic drugs".)
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marker of subsequent response in the treatment of schizophrenia. Neuropsychopharmacology 2010;
35:581.
14. Kinon BJ, Volavka J, Stauffer V, et al. Standard and higher dose of olanzapine in patients with
schizophrenia or schizoaffective disorder: a randomized, double-blind, fixed-dose study. J Clin
Psychopharmacol 2008; 28:3
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15. RoyalThe use of
College ofUpToDate is subject
Psychiatrists. to the Subscription
Consensus statement onand License
high Agreement. medication. CR138,
dose antipsychotic
10 of 25 18/03/16 12:36
Royal College of Psychiatrists, London 2006.

16. UK National Institute for Health and Clinical Excellence Guidelines http://guidance.nice.org.uk
/CG/WaveR/26.
17. Stroup TS, Lieberman JA, McEvoy JP, et al. Effectiveness of olanzapine, quetiapine, risperidone, and
ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical
antipsychotic. Am J Psychiatry 2006; 163:611.
18. Essock SM, Covell NH, Davis SM, et al. Effectiveness of switching antipsychotic medications. Am J
Psychiatry 2006; 163:2090.
19. Jibson MD, Tandon R. Treatment of acute psychotic episodes. In: Schizophrenia: a new guide for
clinicians, Csernansky, JG. (Eds), Marcel Dekker, New York 2001. p.107.
20. Kinon BJ, Basson BR, Gilmore JA, et al. Strategies for switching from conventional antipsychotic drugs
or risperidone to olanzapine. J Clin Psychiatry 2000; 61:833.
21. Stanilla JK, de Leon J, Simpson GM. Clozapine withdrawal resulting in delirium with psychosis: a
report of three cases. J Clin Psychiatry 1997; 58:252.
22. Ahmed S, Chengappa KN, Naidu VR, et al. Clozapine withdrawal-emergent dystonias and
dyskinesias: a case series. J Clin Psychiatry 1998; 59:472.
23. Shiovitz TM, Welke TL, Tigel PD, et al. Cholinergic rebound and rapid onset psychosis following abrupt
clozapine withdrawal. Schizophr Bull 1996; 22:591.
24. Gren JL, Parks JJ, Ghinassi FA, et al. When is antipsychotic polypharmacy supported by research
evidence? Implications for QI. Jt Comm J Qual Patient Saf 2008; 34:571.
25. Barbui C, Signoretti A, Mul S, et al. Does the addition of a second antipsychotic drug improve
clozapine treatment? Schizophr Bull 2009; 35:458.
26. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International
Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003; 60:82.
27. Buckley PF. Treating movement disorders and akathisia as side effects of antipsychotic
pharmacotherapy. J Clin Psychiatry 2008; 69:e14.
28. Dixon L. Dual diagnosis of substance abuse in schizophrenia: prevalence and impact on outcomes.
Schizophr Res 1999; 35 Suppl:S93.
29. Marder SR. Treatment of agitation in patients with schizophrenia. J Clin Psychiatry 2008; 69:e17.
30. Davis JM. Maintenance therapy and the natural course of schizophrenia. J Clin Psychiatry 1985;
46:18.
31. Sikich L, Frazier JA, McClellan J, et al. Double-blind comparison of first- and second-generation
antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment
of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry 2008; 165:1420.
32. Leucht S, Tardy M, Komossa K, et al. Maintenance treatment with antipsychotic drugs for
schizophrenia. Cochrane Database Syst Rev 2012; 5:CD008016.
33. Beck ML, Freihaut B, Henry R, et al. A serum haemagglutinating property dependent upon
polycarboxyl groups. Br J Haematol 1975; 29:149.
34. Wunderink L, Nienhuis FJ, Sytema S, et al. Guided discontinuation versus maintenance treatment in
remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry 2007; 68:654.
35. Wunderink L, Nieboer RM, Wiersma D, et al. Recovery in remitted first-episode psychosis at 7 years of
follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term
Close
follow-up
The of
usea of
2-year randomi
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11 of 25 18/03/16 12:36
36. Harrow M, Jobe TH, Faull RN. Do all schizophrenia patients need antipsychotic treatment continuously
throughout their lifetime? A 20-year longitudinal study. Psychol Med 2012; 42:2145.
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schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). Am J
Psychiatry 2009; 166:675.
38. Keefe RS, Sweeney JA, Gu H, et al. Effects of olanzapine, quetiapine, and risperidone on
neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison. Am J
Psychiatry 2007; 164:1061.
39. Harvey PD, Patterson TL, Potter LS, et al. Improvement in social competence with short-term atypical
antipsychotic treatment: a randomized, double-blind comparison of quetiapine versus risperidone for
social competence, social cognition, and neuropsychological functioning. Am J Psychiatry 2006;
163:1918.
40. Keefe RS, Bilder RM, Davis SM, et al. Neurocognitive effects of antipsychotic medications in patients
with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 2007; 64:633.
41. Sergi MJ, Green MF, Widmark C, et al. Social cognition [corrected] and neurocognition: effects of
risperidone, olanzapine, and haloperidol. Am J Psychiatry 2007; 164:1585.
42. Buchanan RW, Javitt DC, Marder SR, et al. The Cognitive and Negative Symptoms in Schizophrenia
Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive
impairments. Am J Psychiatry 2007; 164:1593.
43. Tuominen HJ, Tiihonen J, Wahlbeck K. Glutamatergic drugs for schizophrenia. Cochrane Database
Syst Rev 2006; :CD003730.
44. Goff DC, Herz L, Posever T, et al. A six-month, placebo-controlled trial of D-cycloserine
co-administered with conventional antipsychotics in schizophrenia patients. Psychopharmacology
(Berl) 2005; 179:144.
45. Kohler CG, Martin EA, Kujawski E, et al. No effect of donepezil on neurocognition and social cognition
in young persons with stable schizophrenia. Cogn Neuropsychiatry 2007; 12:412.
46. Mazeh D, Zemishlani H, Barak Y, et al. Donepezil for negative signs in elderly patients with
schizophrenia: an add-on, double-blind, crossover, placebo-controlled study. Int Psychogeriatr 2006;
18:429.
47. Freudenreich O, Herz L, Deckersbach T, et al. Added donepezil for stable schizophrenia: a double-
blind, placebo-controlled trial. Psychopharmacology (Berl) 2005; 181:358.
48. Sharma T, Reed C, Aasen I, Kumari V. Cognitive effects of adjunctive 24-weeks Rivastigmine
treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind
investigation. Schizophr Res 2006; 85:73.
49. Kumari V, Aasen I, ffytche D, et al. Neural correlates of adjunctive rivastigmine treatment to
antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind fMRI study.
Neuroimage 2006; 29:545.
50. Buchanan RW, Conley RR, Dickinson D, et al. Galantamine for the treatment of cognitive impairments
in people with schizophrenia. Am J Psychiatry 2008; 165:82.
51. Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr
Bull 2009; 35:383.
52. Kessler RC, Nelson CB, McGonagle KA, et al. The epidemiology of co-occurring addictive and mental
disorders: implications for prevention and service utilization. Am J Orthopsychiatry 1996; 66:17.
Close
53. Institute
Theofuse
Medicine. Improving
of UpToDate the Quality
is subject of Health Care
to the Subscription andfor Mental
License and Substance-Use Conditions:
Agreement.
12 of 25 18/03/16 12:36
Quality Chasm Series, National Academy Press, 2006. p.210.
Topic 14805 Version 17.0
Close
13 of 25 18/03/16 12:36
GRAPHICS
Selected adverse effects of antipsychotic medications for

schizophrenia
Weight
Hyper- Prolactin
gain/diabetes EPS/TD Sedation
cholesterolemia elevation
mellitus
First generation agents
Chlorpromazine +++ +++ + ++ +++
Fluphenazine + + +++ +++ +
Haloperidol + + +++ +++ ++
Loxapine ++ ND ++ ++ ++
Perphenazine ++ ND ++ ++ ++
Pimozide + ND +++ ++ +
Thioridazine* ++ ND + +++ +++
Thiothixene ++ ND +++ ++ +
Trifluoperazine ++ ND +++ ++ +
Second generation agents
Aripiprazole + + +
Asenapine ++ ++ ++ ++
Brexpiprazole + + + /+ +
Cariprazine + /+ + /+ +
Clozapine ++++ ++++ /+ /+ +++
Iloperidone ++ ++ /+ /+ +
Lurasidone /+ ++ /+ ++
Olanzapine ++++ ++++ + + ++
Paliperidone +++ + +++ +++ +
Quetiapine +++ +++ /+ /+ ++
Risperidone +++ + +++ +++ +
Ziprasidone /+ /+ + +
Adverse effects may be dose dependent.
EPS: extrapyramidal symptoms; TD: tardive dyskinesia; ND: no data.

* Thioridazine is also associa Close
The also
Clozapine use of UpToDate
causes is subject to the
granulocytopenia orSubscription and License
agranulocytosis Agreement.
in approximately 1 percent of patients
14 of 25 18/03/16 12:36
requiring regular blood cell count monitoring. Clozapine has been associated with excess risk of
myocarditis and venous thromboembolic events including fatal pulmonary embolism. These issues
are addressed in the UpToDate topic review of guidelines for prescribing clozapine section on
adverse effects.
References:
1. The Medical Letter on Drugs and Therapeutics (August 2015); Vol. 57 (1475):116.
www.medicalletter.org.
2. Rummel-Kluge C, et al. Head-to-head comparisons of metabolic side effects of second
generation antipsychotics in the treatment of schizophrenia: a systematic review and
meta-analysis. Schizophr Res 2010; 123:225.
3. Durn CE, Azermai M, Vander Stichele RH. Systematic review of anticholinergic risk scales in
older adults. Eur J Clin Pharmacol 2013; 69:1485.
4. Lexicomp Online. Copyright 1978-2016 Lexicomp, Inc. All Rights Reserved.
Graphic 82533 Version 24.0
Close
15 of 25 18/03/16 12:36
Pharmacology of antipsychotics: Dosing (adult), formulations,

kinetics and potential for drug interactions
Adjustment
Usual of oral dose Usual
Initial
oral dose in older* or maximum
Agent oral dose Formulations
range medically oral dose
(mg/day)
(mg/day) compromised (mg/day)
patients
First-generation antipsychotics (FGAs)
Chlorpromazine 400 to 600 25 to 200 Use low initial 800 Tab, IM

dose and increase
more gradually
Fluphenazine 2 to 15 2 to 10 1 to 2.5 mg daily 12 Tab, IM, LAI, oral

initially, adjust solution
dose gradually
based on
response
Haloperidol 2 to 20 2 to 10 1 to 5 mg daily; 30 Tab, IM, LAI, oral

adjust dose solution
gradually based
on response
Close
16 of 25 18/03/16 12:36
Loxapine 20 to 80 20 Generally follows 100 Capsule; oral

standard adult inhalation for use
dosing, although in healthcare
a dose reduction settings as
may be indicated alternative to IM
in some cases injection.
Oral solution and
IM injection
available in
countries other
than United
States.
Perphenazine 12 to 24 8 to 16 Initiate dose at 8 24 Tab

mg/day and
titrate more
gradually to the
usual adult range
Pimozide 8 to 10 1 to 2 1 mg/day initially 10 Tab

and titrate more 4 (CYP2D6
Close
17 of 25 18/03/16 12:36
metabolizer)
Thiothixene 10 to 20 5 to 10 Use low initial 30 Capsule

(tiotixene) dose and titrate
more gradually to
the usual adult
dose range
Thioridazine 200 to 600 150 Use low initial 600 Tab

dose and titrate
more gradually to
the usual adult
dose range
Trifluoperazine 15 to 20 4 to 10 Initiate dose at 4 40 Tab

mg/day and
titrate more
gradually to the
usual adult range
Second-generation antipsychotics (SGAs)
Aripiprazole 10 to 15 10 to 15 None 30 Tab, ODT, IM,

LAI, oral solution
Aripiprazole
lauroxil LAI
Asenapine 10 to 20 10 None. 20 Sublingual tab

Exception: Use
contraindicated in
severe hepatic
impairment.
Brexpiprazole 2 to 4 0.5 to 1 Dose adjustments 4 Tab

are needed in
renal or hepatic
impairment
Close
18 of 25 18/03/16 12:36
Cariprazine 1.5 to 6 1.5 Not recommended 6 Capsule

in severe renal or
hepatic
impairment
Clozapine 150 to 600 25 to 50 Titrate gradually 900 Tab, ODT, oral

to reduced suspension
maintenance
range of 100 to
150 mg/day;
maximum 300
mg/day.
Lower doses
advised in renal
or hepatic
impairment;
specific dose
adjustment
recommendations
are not available.
Iloperidone 12 to 24 2 Not recommended 24 Tab

in severe hepatic 12 (CYP2D6
impairment poor
metabolizer or
receiving 2D6
inhibitor
cotreatment)
Lurasidone 40 to 80 40 Dose adjustments 160 Tab

20 (renal or are needed in 80 (moderate
hepatic renal and hepatic or severe renal
insufficiency) impairment impairment,
moderate
hepatic
impairment)
40 (severe
hepatic
insufficiency)
Olanzapine 10 to 20 5 to 10 Initially 1.25 to 30 Tab, ODT, IM, LAI

Close
19 of 25 18/03/16 12:36
typical
maintenance 5
mg/day;
maximum 10
mg/day
Paliperidone 6 to 12 6 Older adults or 12 ER tab, LAI

renal impairment:
3 mg/day
Quetiapine 150 to 750 50 Initially 25 to 50 750 Tab, ER tab

(immediate mg/day; use (immediate
release) substantially release)
400 to 800 lower 800 (extended
(extended maintenance release)
release) dose.
Dose adjustment
needed in hepatic
impairment .
Risperidone 2 to 6 1 to 2 Initially 0.25 to 8 Tab, ODT, LAI,

0.5 mg/day; oral solution
typical
maintenance 1
mg/day;
maximum 2
mg/day.
Dose adjustments
are needed in
renal and hepatic
impairment .
Ziprasidone 40 to 160 40 to 80 Lower doses 200 Capsule, IM

advised in hepatic
impairment;
specific
adjustment
recommendations
are not available
Important note: Doses shown are total daily dose, oral administration, for maintenance
treatment of schizophrenia in otherwise healthy adults. The dosing and other information
provided in this table differs from dosing used in management of behavioral symptoms
Close of
dementia in older adults; in general these medications are not recommended for that use. For
20 of 25 18/03/16 12:36
additional information, refer to the relevant UpToDate clinical topics and the Lexicomp drug
monographs included within UpToDate.
ODT: orally dissolving tablet; Tab: tablet; ER tab: extended-release tablet; IM: short-acting
intramuscular injection; LAI: long-acting injectable (eg, depot); CYP: cytochrome P-450; P-gp:
membrane P-glycoprotein transporters; UGT-glucuronidation: uridine 5'diphosphate-
glucuronyltransferases.
* First- and second-generation antipsychotics are included on the Beers list of medications to be
used with caution in older adults and should in general be avoided except for schizophrenia and
bipolar disorder. J Am Geriatr Soc 2015; 63:2227.
First-generation antipsychotics (FGAs) undergo extensive hepatic metabolism; levels may be
elevated in hepatic impairment necessitating dose reduction and more gradual dose titration to
avoid toxicity. FGAs should be used with caution at significantly reduced doses or avoided in severe
hepatic impairment.
Usual maximum total oral daily dose for maintenance treatment of schizophrenia in adult patients
without significant comorbidity. Doses shown may not be the maximum dose used in some clinical
trials or in exceptional patients.
Dose adjustments of several antipsychotic medications listed in this table are recommended in
presence of strong or moderate inhibitors or inducers of CYP drug metabolism; for specific
recommendations refer to the individual Lexicomp drug monographs.
Only potent to moderate inhibitor effects are listed in this table. For additional information
including moderate to weak inhibitor or inducer effects, and to determine specific drug interactions,
refer to individual drug monographs section on drug interactions and the Lexi-Interact program
included with UpToDate.
Smoking may decrease blood concentrations of antipsychotics primarily metabolized by CYP1A2.
For specific dose adjustments in setting of renal or hepatic impairment, refer to Lexicomp drug
monograph.
Active metabolites of cariprazine are equipotent to cariprazine. Due to the long half-life of
cariprazine and active metabolites, changes in dose will not reach plasma steady-state for several
weeks or months.
Prepared with data from:

1. US product information (available online at http://dailymed.nlm.nih.gov.ezproxy.usach.cl
/dailymed/about.cfm) and Health Canada product monograph (available online at
http://webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp).
2. Lexicomp Online. Copyright 1978-2016 Lexicomp, Inc. All Rights Reserved.
3. Wynn GH, et al (eds) Clinical Manual of Drug Interaction Principles for Medical Practice APA
publishing, Washington DC. Copyright 2009.
Close
21 of 25 18/03/16 12:36
Antipsychotics for initial management of the acutely agitated

adult patient with psychosis
Maximum
Time to peak
Initial initial
Frequency plasma
Formulation Route dose dose per
(hours) concentration
(mg) 24 hours
(hours)
(mg)
First-generation agents
Haloperidol Short-acting IM, IV 2 to 5 0.5 to 2* 20 0.5 to 1

lactate injection
Oral solution PO 0.5 to 5 6 30 2
Droperidol Injection (short- IM, IV 2.5 to 5 2 to 4* 40 0.5

acting)
Fluphenazine Short-acting IM 1.25 6 10 ND

hydrochloride
injection
Oral solution PO 1 to 2.5 6 10 3
Chlorpromazine Injection (short- IM, IV 25 1 to 4 200 0.5
Close
22 of 25 18/03/16 12:36
Second-generation agents
Aripiprazole Injection (short- IM 9.75 2 30 1

acting)
Disintegrating PO 10 to 15 2 30 3 to 5
tablet, oral
solution
Olanzapine Injection (short- IM 5 to 10 2 to 4 30 0.25 to 0.75

acting)
Disintegrating PO 5 to 10 0.5 to 2 20 5
tablet
Risperidone Disintegrating PO 1 to 2 0.5 to 2 4 1.5

tablet, oral
solution
Ziprasidone Short-acting IM 10 to 20 2 to 4 40 0.5 to 1

mesylate
injection
The approach to pharmacologic treatment of the acutely agitated patient, including specific
medication choices and combinations depending upon presentation (eg, toxic ingestion,
withdrawal syndrome, or known psychiatric history) is provided in the accompanying topic
reviews and in an algorithm.
Dose reduction by one-half is needed for older adults, debilitated patients, and if used in
combination with other sedation. Refer to accompanying text for discussion of
electrocardiograph and other monitoring for agents known to cause prolongation of the
QTc interval.
IM: intramuscular; IV: intravenous; EPS: extrapyramidal symptoms; PO: per os (by mouth); ND:
no data.
* It may be necessary to repeat initial dose or fraction thereof after 15 to 20 minutes in patients
with severe agitation until de Close
23 of 25 18/03/16 12:36
Selected patients without schizophrenia may need a higher cumulative haloperidol dose (eg, up to
30 mg) during the first 24 hours of treatment to achieve and maintain adequate sedation.
Close
24 of 25 18/03/16 12:36
Disclosures
Disclosures: T. Scott Stroup, MD, MPH Research/Grant/Clinical Trial Support: Auspex [Tardive dyskinesia (Deutetrabenazine)].
Other Financial Interest (CME support): Genentech [Schizophrenia (Bitopertin)]. Stephen Marder, MD Grant/Research/Clinical Trial
Support: Forum; Neurocrine [schizophrenia and tardive dyskinesia]. Consultant/Advisory Boards: Abbvie; Takeda; Roche; Lundbeck;
Otsuka; Allergan; Teva [schizophrenia (brexpiprazole, cariprazine)]. Murray B Stein, MD, MPH Grant/Research/Clinical Trial
Support: Janssen [social anxiety disorder]. Consultant/Advisory Boards: Janssen [anxiety and traumatic stress]; Tonix [anxiety and
traumatic stress]; Pfizer [anxiety and traumatic stress]. Richard Hermann, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately
referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
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Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment

Authors Section Editor Deputy Editor

INTRODUCTION Schizophrenia is a psychiatric disorder involving chronic or recurrent psychosis. It is

Body mass index (BMI)

Signs of a movement disorder:

Extrapyramidal symptoms (EPS): akathisia, parkinsonism, dystonias

INITIAL MANAGEMENT OF REFRACTORY SYMPTOMS Patients should be observed on a stable dose

Administration Two basic strategies for changing antipsychotics are [19,20]:

TREATMENT-RESISTANT SCHIZOPHRENIA Patients with schizophrenia who respond inadequately to

manifestations, course, assessment and diagnosis".)

Psychosis Psychotic symptoms of schizophrenia, such as frightening delusions, suspiciousness, and

A combination of haloperidol 5 mg, lorazepam 2 mg, and benztropine 1 mg given intramuscularly

Akathisia from any IM antipsychotic can contribute to agitation.

Treatment of cognitive impairment Improving cognitive impairment has increasingly become an

Basics topics (see "Patient information: Schizophrenia (The Basics)")

SUMMARY AND RECOMMENDATIONS

Signs of a movement disorder including extrapyramidal symptoms and tardive dyskinesia

Symptoms of metabolic syndrome including measurements of body mass index, waist

Clozapine. (See "Treatment-resistant schizophrenia", section on 'Clozapine' and "Guidelines for

Use of UpToDate is subject to the Subscription and License Agreement.

Royal College of Psychiatrists, London 2006.

Quality Chasm Series, National Academy Press, 2006. p.210.

Topic 14805 Version 17.0

Selected adverse effects of antipsychotic medications for

First generation agents

Chlorpromazine +++ +++ + ++ +++

Fluphenazine + + +++ +++ +

Haloperidol + + +++ +++ ++

Thioridazine* ++ ND + +++ +++

Second generation agents

Clozapine ++++ ++++ /+ /+ +++

Olanzapine ++++ ++++ + + ++

Paliperidone +++ + +++ +++ +

Quetiapine +++ +++ /+ /+ ++

Risperidone +++ + +++ +++ +

Adverse effects may be dose dependent.

EPS: extrapyramidal symptoms; TD: tardive dyskinesia; ND: no data.

Graphic 82533 Version 24.0

Pharmacology of antipsychotics: Dosing (adult), formulations,

First-generation antipsychotics (FGAs)

Chlorpromazine 400 to 600 25 to 200 Use low initial 800 Tab, IM

Fluphenazine 2 to 15 2 to 10 1 to 2.5 mg daily 12 Tab, IM, LAI, oral

Haloperidol 2 to 20 2 to 10 1 to 5 mg daily; 30 Tab, IM, LAI, oral

Loxapine 20 to 80 20 Generally follows 100 Capsule; oral

Perphenazine 12 to 24 8 to 16 Initiate dose at 8 24 Tab

Pimozide 8 to 10 1 to 2 1 mg/day initially 10 Tab

Thiothixene 10 to 20 5 to 10 Use low initial 30 Capsule

Thioridazine 200 to 600 150 Use low initial 600 Tab

Trifluoperazine 15 to 20 4 to 10 Initiate dose at 4 40 Tab

Second-generation antipsychotics (SGAs)

Aripiprazole 10 to 15 10 to 15 None 30 Tab, ODT, IM,

Asenapine 10 to 20 10 None. 20 Sublingual tab

Brexpiprazole 2 to 4 0.5 to 1 Dose adjustments 4 Tab

Cariprazine 1.5 to 6 1.5 Not recommended 6 Capsule

Clozapine 150 to 600 25 to 50 Titrate gradually 900 Tab, ODT, oral

Iloperidone 12 to 24 2 Not recommended 24 Tab

Lurasidone 40 to 80 40 Dose adjustments 160 Tab

Olanzapine 10 to 20 5 to 10 Initially 1.25 to 30 Tab, ODT, IM, LAI

Paliperidone 6 to 12 6 Older adults or 12 ER tab, LAI

Quetiapine 150 to 750 50 Initially 25 to 50 750 Tab, ER tab

Risperidone 2 to 6 1 to 2 Initially 0.25 to 8 Tab, ODT, LAI,