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Official reprint from UpToDate www.uptodate.com ©2014 UpToDate

AuthorsT. Scott Stroup, MD, MPHStephen Marder, MD

Section EditorMurray B Stein, MD, MPH

Deputy EditorRichard Hermann, MD

Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jun 2014. | This topic last updated: Dec 20, 2013.

INTRODUCTION — Schizophrenia is a psychiatric disorder involving chronic or recurrent psychosis. It is commonly associated with impairments in social and occupationalfunctioning [1]. It is among the most disabling and economically catastrophic medical disorders, ranked by the World Health Organization as one of the top ten illnessescontributing to the global burden of disease [2].

Antipsychotic medications are first­line medication treatment for schizophrenia. They have been shown in clinical trials to be effective in treating symptoms and behaviorsassociated with the disorder. Antipsychotic medications have significant side effects; assessment and management of these adverse effects are an important part oftreatment. Evidence­based 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 long­acting antipsychotics andmanagement of side effects during pharmacotherapy for schizophrenia; the epidemiology, pathogenesis, clinical presentation, epidemiology, clinical manifestations, anddiagnosis of schizophrenia; psychosocial interventions for schizophrenia; and common comorbid presentations of schizophrenia. (See "Pharmacotherapy for schizophrenia:Long­acting 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 "Co­occurring schizophrenia and substance use disorder: Epidemiology, pathogenesis, clinical manifestations, 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 priorhistory 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 andbehaviors. (See "Schizophrenia: Clinical manifestations, course, assessment, and diagnosis", section on 'Clinical manifestations'.)

Pre­treatment assessment — When feasible, patients who are started on an antipsychotic medication should receive a baseline physical examination with a neurologicalexam. Particular attention should be focused on factors that may be affected adversely by antipsychotic medication: (See "Pharmacotherapy for schizophrenia: Side effectmanagement".)

When feasible, laboratory evaluations should be initiated before starting an antipsychotic. With the exception of patients treated with clozapine, the antipsychotic can usuallybe started before the results of laboratory tests are available.

Antipsychotic drug efficacy and selection — Antipsychotic drugs are first­line treatment for schizophrenia. Randomized trials have shown that antipsychotics reducepositive symptoms of schizophrenia, such as hallucinations, delusions, and suspiciousness, compared to placebo [3]. Antipsychotics eliminate or reduce these symptoms toa tolerable level in about 70 percent of patients with schizophrenia [4].

With the exception of clozapine, careful systematic reviews and meta­analyses have not found convincing evidence that any of the antipsychotics are more effective thanany other for acute schizophrenia [5]. Clozapine is more effective for patients who do not respond fully to other antipsychotics, but due to increased risk of agranulocytosis isreserved for those who do not respond well to or cannot tolerate other antipsychotics. (See 'Treatment­resistant schizophrenia' below.)

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, theselection 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 forschizophrenia: Side effect management".)

Antipsychotic drug categories — Antipsychotic medications are commonly grouped into two categories, with “second­generation” (or “atypical”) applied to clozapine andall antipsychotics first marketed after clozapine was approved in 1989, and “first­generation” applied to antipsychotics marketed previously. Recent clinical research, however,has strongly suggested that the distinction between first­ and second­generation antipsychotics has questionable validity and is confusing [5]. The pharmacologic properties,therapeutic effects, and adverse effects are not distinct between and are heterogeneous within the groups. Nevertheless, the terms first­ and second­generation antipsychoticare still in widespread use. A valid distinction is that the newer (second­generation) 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, andiloperidone need to be increased gradually before reaching a therapeutic dose. The timeframe for titration differs for each drug and also depends on the individual patient’stolerance of the drug’s 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).

®®

Body mass index (BMI)

Waist circumference

Heart rate

Blood pressure

Signs of a movement disorder:

Extrapyramidal symptoms (EPS): akathisia, parkinsonism, dystonias•

Tardive dyskinesia: abnormal movements of the face, peri­oral areas, tongue, extremities•

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.

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Because identifying the appropriate dose range can be difficult in the pre­marketing phases of drug development, the antipsychotic doses listed (table 2) deviate somewhatfrom those approved by the US Food and Drug Administration, reflecting more recent research findings or clinical experience. Examples include:

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 themedication 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 whichthe 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 improvementon 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, minimalsedation, 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 dosecan 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 ofEPS.

Because of dose­related toxicities, antipsychotics should be used at the lowest dose that is effective for an individual. The toxicities of antipsychotic drugs typically increasewith higher doses while therapeutic effects can reach a maximum. At high doses, the adverse effects of an antipsychotic may surpass the marginal benefit of dosageincreases. As a result, increasing the dose of antipsychotic for a patient who is already experiencing significant EPS is unlikely to result in additional symptom reduction [6­8].

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. Mostpatients who will improve on an antipsychotic show the most rapid improvement in the first two weeks [9]. 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 bereduced [10]. Hallucinations or delusions may be less frightening or the patient may find that they can distract themselves by focusing their attention elsewhere [11].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 thedrug is ineffective. The duration of the trial will vary depending on a number of factors:

Dose adjustments — In cases of nonresponse or partial response, the antipsychotic dose can be gradually increased toward the high end of the recommended range (table2).

Most careful studies of doses above the recommended range have not found higher doses to be more effective than the maximal recommended dose [13,14]. If used, trials ofhigher doses should be time limited, with reassessment planned within three months. Unless clear evidence of improvement is seen, high doses should not be continued [15].

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 USeffectiveness study of antipsychotic treatment for schizophrenia, the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE), patients who gained weight during thefirst phase of antipsychotic treatment frequently lost weight when they were changed to ziprasidone, an antipsychotic that is not associated with weight gain [16].

Switching antipsychotics is less clearly beneficial when the initial medication lacked effectiveness. Most studies have shown that poor responders to one antipsychotic arelikely to be poor responders to another antipsychotic except when the second agent is clozapine. (See 'Treatment­resistant 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 whowere randomly assigned to continue the same antipsychotic had better outcomes than patients who were randomly assigned to change antipsychotics [17]. (See'Administration' below.)

Administration — Two basic strategies for changing antipsychotics are [18,19]:

Discontinuation of antipsychotic medications is generally well tolerated, except for clozapine, for which both cholinergic rebound and withdrawal­emergent movement disordershave been reported [20­22]. A slow taper of clozapine over one to two weeks is recommended. Chlorpromazine and thioridazine can also cause cholinergic rebound andshould 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 evidencesupports this practice [23]. Although some randomized trials indicated that augmentation of clozapine with another antipsychotic may have some benefit, a meta­analysis ofthis practice found the supporting evidence to be weak [24].

TREATMENT­RESISTANT SCHIZOPHRENIA — Patients with schizophrenia who respond inadequately to an initial antipsychotic, dose adjustments, or a change inantipsychotics are classified as having treatment­resistant schizophrenia. The efficacy of interventions for treatment­resistant schizophrenia, including clozapine, isdiscussed separately. Guidelines for clozapine prescribing, dosing, monitoring, and side­effect management are described separately. (See "Treatment­resistantschizophrenia" 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 andschizoaffective disorder at high risk for suicide [25]. A patient with schizophrenia who has persistent suicidal ideation warranting clinician concern may benefit from a trial ofclozapine. Guidelines for clozapine prescribing, dosing, monitoring, and side­effect management are described separately. Management of suicidal patients is described

Haloperidol is effective and most useful at doses drastically below the FDA­specified maximum of 100 mg/day. Optimal haloperidol dosages are usually below 10mg/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.

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 [9].

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 willhave a robust response [12]. The 2009 Schizophrenia PORT recommends that trials last for two to six weeks. This timeframe will be slightly longer for antipsychoticssuch as iloperidone and quetiapine, which require slow titration.

A standard cross­titration for a stable patient: Simultaneous taper of the current medication with titration of the replacement drug in three to four steps over several daysto 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 itstarget dose, the first medication may be gradually decreased and discontinued. In most cases this change can be managed in one to two weeks.

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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, orpsychosis.

Extrapyramidal symptoms — Akathisia can be difficult to distinguish from psychotic agitation when patients are unable to describe the experience of restlessness [26].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 [27]. 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 ahistory, physical exam, and toxicology. (See 'Pharmacotherapy for comorbid disorders' below and "Co­occurring schizophrenia and substance use disorder: Epidemiology,pathogenesis, clinical manifestations, 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 ofadministration depend on a number of considerations including the urgency of calming the patient and the cooperativeness of the patient [28]. As noted below, the choice ofan 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 withoutinducing sedation.

Treatment — Although antipsychotic medications can take days to weeks before having a robust antipsychotic effect, they generally have a calming effect within minutes foragitated patients. The route of administration influences time to onset, as described below (table 3). (See "First­generation antipsychotic medications: Pharmacology,administration, and comparative side effects" and "Second­generation antipsychotic medications: Pharmacology, administration, and comparative side effects".)

Although repeat administration of an oral or intramuscular antipsychotic is common when the prior dose does not sufficiently reduce agitation, the overall antipsychotic doseshould be limited, because these medications can cause significant side effects such as hypotension, EPS, and sedation, particularly at high doses over a brief period oftime [9]. 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 failto respond to one or two doses of an antipsychotic for agitation. Lorazepam can be administered as 1 to 2 mg orally or 0.5 to 1 mg intramuscularly for calming.

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 [29]. At the same time, younger patients and first episode patients have a greater vulnerability to side effectssuch as weight gain and extrapyramidal side effects (EPS) [30]. Since many first episode patients are also reluctant to take an antipsychotic, it is important to minimizeadverse effects.

The Schizophrenia Patient Outcomes Research Team (PORT) recommended treating first episodes with antipsychotics other than clozapine or olanzapine. Both of thesemedications 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 first­episode patients receive antipsychotic doses in the lower half of the recommended dose range [3]. As examples, a first­episode 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 mayrequire 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 whichpsychotic 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 self­determination, 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]. Thelowest effective dose that achieves therapeutic goals should be used. Patients should participate in the clinical decision­making regarding the duration of antipsychotic drugtreatment.

Multiple randomized trials have found that maintenance antipsychotic medication reduces the risk of relapse over a period of up to two years. A meta­analysis of 6493patients with schizophrenia in 65 randomized trials of 7 to 12 months duration found that patients who continued on an antipsychotic experienced a lower relapse ratecompared to patients withdrawn from an antipsychotic and receiving placebo (27 versus 64 percent; number needed to treat to benefit = 3, 95% CI 2–3) [31]. Other studies ofup to two years have found similar results [32].

A seven­year follow­up assessment of patients randomly assigned to either a dose reduction strategy or to maintenance antipsychotic treatment found results that conflictwith the studies of up to two years. Two reports that follow describe an intervention and follow­up assessment of patients who experienced a first episode of psychosis andsubsequently met criteria for remission prior to enrollment in the trial [33,34].

Standard oral formulations: Although many clinicians tend to favor sedating antipsychotics for agitated patients, non­sedating agents can also be effective for reducingagitation. 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, and aripiprazole. These formulations are helpful when apatient 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.

Short­acting intramuscular (IM) injectable formulations (eg, haloperidol, olanzapine, aripiprazole, and ziprasidone): Olanzapine 5 or 10 mg administered intramuscularly isa good choice under most circumstances. IM haloperidol is effective but should be given with benztropine or diphenhydramine to reduce the risk of severe EPS includingdystonias.

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 30minutes following IM administration. Calming effects may take 30 to 60 minutes following oral administration.

•

The initial trial randomly assigned 128 patients to continue maintenance treatment or to a dose reduction strategy [33]. After two years, patients assigned to the dosereduction strategy had a higher rate of relapse, without offsetting advantages, compared to patients continuing on maintenance treatment.

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More studies of longer term outcomes of maintenance treatment versus dose reduction are needed before we would suggest an approach other than indefinite continuation ofmaintenance 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 [35].

Other considerations regarding selection of antipsychotic medication for maintenance treatment mirror those for pharmacotherapy during the acute phase. (See 'Antipsychoticdrug efficacy and selection' above.)

Medication adherence — Long­acting injectable antipsychotics may be useful for patients with schizophrenia who experience frequent relapses due to non­adherence toantipsychotic medications. They also may be helpful for patients who will not take oral antipsychotics regularly. (See "Pharmacotherapy for schizophrenia: Long­actinginjectable antipsychotic drugs".)

Other strategies to promote better adherence to antipsychotics include simplifying medication regimens (eg, fewer medications, fewer pills, fewer daily doses) and activeengagement 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 suggestthat antipsychotic medication may improve cognition when received early in the course of schizophrenia [36,37]. Studies of patients with chronic schizophrenia have generallyfound less improvement in cognition during antipsychotic treatment [37­40]. Trials of other medications (including n­methyl­d­aspartate (NMDA) glutamatergic receptoragonists, glycine, D­serine, ampakine CX516, D­cycloserine, donepezil, rivastigmine, and galantamine) have failed to show significant benefit [41­49].

Pharmacotherapy for comorbid disorders — Depressive disorders and anxiety disorders can be challenging to diagnose in patients with schizophrenia. A primary comorbiddisorder needs to be distinguished from symptoms of schizophrenia, antipsychotic drug side effects, and other clinical presentations. Properly diagnosed, however, thesesyndromes can respond to antidepressant and anxiolytic medications [50]. (See "Depression in schizophrenia" and "Anxiety in schizophrenia".)

Substance abuse and dependence occur at a high prevalence in schizophrenia [51]. 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 relapsecompared to either disorder individually [52]. Integrated treatment strategies for dual diagnosis that include pharmacotherapy have been developed for individuals withschizophrenia and SUDs. (See "Co­occurring schizophrenia and substance use disorder: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)

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SUMMARY AND RECOMMENDATIONS

A subsequent assessment at seven years follow­up included 103 of the 128 patients (81 percent) who participated in the trial [34]. Patients who had originally beenassigned to the dose reduction strategy experienced a higher rate of recovery (ie, symptomatic and functional remission) compared to patients originally assigned tomaintenance treatment.

th th

th th

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

Patients treated with an antipsychotic for schizophrenia should be assessed prior to treatment if possible and at regular intervals for: (See 'Pre­treatment 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 first­line medication treatment for acute and maintenance phase treatment for schizophrenia (Grade 1A). (See'Antipsychotic drug efficacy and selection' above.)

For patients with schizophrenia who have recovered from an acute psychotic episode, we suggest that antipsychotic medication should be continued indefinitely at thelowest effective dose that achieves therapeutic goals (Grade 2C). This approach is suggested even for patients who have achieved remission from a first psychoticepisode. (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 effectprofiles of antipsychotic drugs. With the exception of clozapine for patients with refractory symptoms, there is not convincing evidence to favor one antipsychotic overthe others based on efficacy. (See 'Antipsychotic drug efficacy and selection' above.)

Because olanzapine is associated with significant weight gain and metabolic adverse effects, leading guidelines state that it should not be used as a first­lineagent for first­episode patients, but should be considered for patients who fail treatment with a first­line 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 improvedefficacy, with the exception of clozapine. (See 'Changing to another antipsychotic' above.)

•

Clozapine. (See "Treatment­resistant 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 twotrials 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 astandard oral formulation, rapid dissolving, or intramuscularly injected antipsychotic, depending on the level of patient participation. Other causes of agitation should beruled out, including akathisia and substance abuse or withdrawal. (See 'Management of agitation' above.)

Long­acting injectable (LAI) antipsychotic medication may be useful for patients with schizophrenia when non­adherence 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 mgintramuscularly every two weeks. Extrapyramidal symptoms can be prominent at higher doses. (See 'Medication adherence' above and "Pharmacotherapy for

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REFERENCES

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM­5), American Psychiatric Association, Arlington, VA 2013.2. Murray CJL, Lopez AD. The Global Burden of Disease, Harvard University Press, Cambridge, MA 1996. p.21.3. Buchanan RW, Kreyenbuhl J, Kelly DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr

Bull 2010; 36:71.4. Dixon LB, Lehman AF, Levine J. Conventional antipsychotic medications for schizophrenia. Schizophr Bull 1995; 21:567.5. Leucht S, Corves C, Arbter D, et al. Second­generation versus first­generation antipsychotic drugs for schizophrenia: a meta­analysis. Lancet 2009; 373:31.6. McEvoy JP, Hogarty GE, Steingard S. Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose.

Arch Gen Psychiatry 1991; 48:739.7. Kapur S, Zipursky R, Jones C, et al. Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double­blind PET study of first­episode

schizophrenia. Am J Psychiatry 2000; 157:514.8. Stone JM, Davis JM, Leucht S, Pilowsky LS. Cortical dopamine D2/D3 receptors are a common site of action for antipsychotic drugs­­an original patient data meta­

analysis of the SPECT and PET in vivo receptor imaging literature. Schizophr Bull 2009; 35:789.9. Agid O, Kapur S, Arenovich T, Zipursky RB. Delayed­onset hypothesis of antipsychotic action: a hypothesis tested and rejected. Arch Gen Psychiatry 2003; 60:1228.10. Mizrahi R, Kiang M, Mamo DC, et al. The selective effect of antipsychotics on the different dimensions of the experience of psychosis in schizophrenia spectrum

disorders. Schizophr Res 2006; 88:111.11. Mizrahi R, Bagby RM, Zipursky RB, Kapur S. How antipsychotics work: the patients' perspective. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:859.12. Kinon BJ, Chen L, Ascher­Svanum H, et al. Early response to antipsychotic drug therapy as a clinical marker of subsequent response in the treatment of schizophrenia.

Neuropsychopharmacology 2010; 35:581.13. Kinon BJ, Volavka J, Stauffer V, et al. Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: a randomized, double­blind,

fixed­dose study. J Clin Psychopharmacol 2008; 28:392.14. Royal College of Psychiatrists. Consensus statement on high dose antipsychotic medication. CR138, Royal College of Psychiatrists, London 2006.15. UK National Institute for Health and Clinical Excellence Guidelines http://guidance.nice.org.uk/CG/WaveR/26.16. 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; 163:611.17. Essock SM, Covell NH, Davis SM, et al. Effectiveness of switching antipsychotic medications. Am J Psychiatry 2006; 163:2090.18. 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.107.19. Kinon BJ, Basson BR, Gilmore JA, et al. Strategies for switching from conventional antipsychotic drugs or risperidone to olanzapine. J Clin Psychiatry 2000; 61:833.20. Stanilla JK, de Leon J, Simpson GM. Clozapine withdrawal resulting in delirium with psychosis: a report of three cases. J Clin Psychiatry 1997; 58:252.21. Ahmed S, Chengappa KN, Naidu VR, et al. Clozapine withdrawal­emergent dystonias and dyskinesias: a case series. J Clin Psychiatry 1998; 59:472.22. Shiovitz TM, Welke TL, Tigel PD, et al. Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal. Schizophr Bull 1996; 22:591.23. Gören 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;

34:571.24. Barbui C, Signoretti A, Mulè S, et al. Does the addition of a second antipsychotic drug improve clozapine treatment? Schizophr Bull 2009; 35:458.25. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003;

60:82.26. Buckley PF. Treating movement disorders and akathisia as side effects of antipsychotic pharmacotherapy. J Clin Psychiatry 2008; 69:e14.27. Dixon L. Dual diagnosis of substance abuse in schizophrenia: prevalence and impact on outcomes. Schizophr Res 1999; 35 Suppl:S93.28. Marder SR. Treatment of agitation in patients with schizophrenia. J Clin Psychiatry 2008; 69:e17.29. Davis JM. Maintenance therapy and the natural course of schizophrenia. J Clin Psychiatry 1985; 46:18.30. Sikich L, Frazier JA, McClellan J, et al. Double­blind comparison of first­ and second­generation antipsychotics in early­onset schizophrenia and schizo­affective

disorder: findings from the treatment of early­onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry 2008; 165:1420.31. Leucht S, Tardy M, Komossa K, et al. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2012; 5:CD008016.32. Beck ML, Freihaut B, Henry R, et al. A serum haemagglutinating property dependent upon polycarboxyl groups. Br J Haematol 1975; 29:149.33. Wunderink L, Nienhuis FJ, Sytema S, et al. Guided discontinuation versus maintenance treatment in remitted first­episode psychosis: relapse rates and functional

outcome. J Clin Psychiatry 2007; 68:654.34. Wunderink L, Nieboer RM, Wiersma D, et al. Recovery in remitted first­episode psychosis at 7 years of follow­up of an early dose reduction/discontinuation or

maintenance treatment strategy: long­term follow­up of a 2­year randomized clinical trial. JAMA Psychiatry 2013; 70:913.35. Harrow M, Jobe TH, Faull RN. Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20­year longitudinal study. Psychol

Med 2012; 42:2145.36. Davidson M, Galderisi S, Weiser M, et al. Cognitive effects of antipsychotic drugs in first­episode schizophrenia and schizophreniform disorder: a randomized, open­

label clinical trial (EUFEST). Am J Psychiatry 2009; 166:675.37. Keefe RS, Sweeney JA, Gu H, et al. Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double­blind 52­

week comparison. Am J Psychiatry 2007; 164:1061.38. Harvey PD, Patterson TL, Potter LS, et al. Improvement in social competence with short­term atypical antipsychotic treatment: a randomized, double­blind comparison

of quetiapine versus risperidone for social competence, social cognition, and neuropsychological functioning. Am J Psychiatry 2006; 163:1918.39. 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; 64:633.40. Sergi MJ, Green MF, Widmark C, et al. Social cognition [corrected] and neurocognition: effects of risperidone, olanzapine, and haloperidol. Am J Psychiatry 2007;

164:1585.41. 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; 164:1593.42. Tuominen HJ, Tiihonen J, Wahlbeck K. Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev 2006; :CD003730.43. Goff DC, Herz L, Posever T, et al. A six­month, placebo­controlled trial of D­cycloserine co­administered with conventional antipsychotics in schizophrenia patients.

Psychopharmacology (Berl) 2005; 179:144.44. Kohler CG, Martin EA, Kujawski E, et al. No effect of donepezil on neurocognition and social cognition in young persons with stable schizophrenia. Cogn

schizophrenia: Long­acting injectable antipsychotic drugs".)

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Neuropsychiatry 2007; 12:412.45. Mazeh D, Zemishlani H, Barak Y, et al. Donepezil for negative signs in elderly patients with schizophrenia: an add­on, double­blind, crossover, placebo­controlled study.

Int Psychogeriatr 2006; 18:429.46. Freudenreich O, Herz L, Deckersbach T, et al. Added donepezil for stable schizophrenia: a double­blind, placebo­controlled trial. Psychopharmacology (Berl) 2005;

181:358.47. Sharma T, Reed C, Aasen I, Kumari V. Cognitive effects of adjunctive 24­weeks Rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo­

controlled, double­blind investigation. Schizophr Res 2006; 85:73.48. Kumari V, Aasen I, ffytche D, et al. Neural correlates of adjunctive rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo­controlled, double­

blind fMRI study. Neuroimage 2006; 29:545.49. Buchanan RW, Conley RR, Dickinson D, et al. Galantamine for the treatment of cognitive impairments in people with schizophrenia. Am J Psychiatry 2008; 165:82.50. Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009; 35:383.51. Kessler RC, Nelson CB, McGonagle KA, et al. The epidemiology of co­occurring addictive and mental disorders: implications for prevention and service utilization. Am

J Orthopsychiatry 1996; 66:17.52. Institute of Medicine. Improving the Quality of Health Care for Mental and Substance­Use Conditions: Quality Chasm Series, National Academy Press, 2006. p.210.

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GRAPHICS

Selected adverse effects of antipsychotic medications for schizophrenia

Weight

gain/diabetesmellitus

Hyper­cholesterolemia

EPS/TDProlactinelevation

Sedation

Anti­cholinergic

sideeffects

Orthostatichypotension

QTcprolongation

First generation agents

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

Fluphenazine + + +++ +++ + – – ND

Haloperidol + + +++ +++ ++ – – +

Loxapine ++ ND ++ ++ ++ + + +

Perphenazine ++ ND ++ ++ ++ – – ND

Pimozide + ND +++ ++ + + + ++

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

Thiothixene ++ ND +++ ++ + – + +

Trifluoperazine ++ ND +++ ++ + – + ND

Second generation agents

Aripiprazole – – + – + – – +

Asenapine + – + ++ ++ – + +

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 associated with dose­dependent retinitis pigmentosa. Refer to text.• Clozapine also causes granulocytopenia or agranulocytosis in approximately 1 percent of patients requiring regular blood cell count monitoring.

Adapted from:1. Treatment Guidelines from The Medical Letter, August 2010; Vol. 8 (96):61. www.medicalletter.org.

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Pharmacology of antipsychotics: Dosing (adult), formulations, kinetics and potential for drug interactions

Agent

Usual oraldoserange

(mg/day)

Initial oraldose

(mg/day)

Usualmaximumoral dose(mg/day)*

Formulations

Half­life afteroral

administration(hours)

Primarymetabolism

Enzyme(s)inhibited(see note)

First generation antipsychotics (FGAs)

Chlorpromazine 400 to 600 25 to 200 800 Tab, IM 30 CYP2D6, otherCYPs and UGT­glucuronidationto active andinactivemetabolites

CYP2D6

Fluphenazine 2 to 15 2 to 10 12 Tab, IM, LAI, oralsolution

33 CYP2D6 CYP2D6

Haloperidol 2 to 20 2 to 10 30 Tab, IM, LAI, oralsolution

20 CYPs 2D6, 3A4and UGT­glucuronidation;somemetabolitespotentially activeor toxic

CYPs 2D6, 3A4(moderate)

Loxapine 20­80 20 100 Capsule; oralinhalation for usein healthcaresettings asalternative to IMinjection

Oral solution andIM injectionavailable incountries otherthan United States

12 CYPs 1A2, 2D6,3A4 and UGT­glucuronidationto active andinactivemetabolites

None

Perphenazine 12 to 24 8 to 16 24 Tab 9­12 CYPs 2D6, 3A4and other CYPsto active andinactivemetabolites

CYP2D6

Pimozide 8 to 10 1 to 2 10

4 (CYP2D6 poormetabolizer)

Tab 55 CYPs 1A2, 2D6,3A4 and others

CYP2D6

Thiothixene(tiotixene)

10 to 20 5 to 10 30 Capsule 33 CYP1A2 andother CYPs

None

Thioridazine 200 to 600 150 600 Tab 21­25 CYP2D6 andother CYPs toactive(mesoridazine)and inactivemetabolites

CYP2D6

Trifluoperazine 15 to 20 4 to 10 40 Tab 22 CYP1A2 None

Second generation antipsychotics (SGAs)

Aripiprazole 10 to 15 10 to 15 30 Tab, ODT, IM, LAI,oral solution

75­94 CYPs 2D6 and3A4 to activeand inactivemetabolites

None

Asenapine 10 to 20 10 20 Sublingual tab 24 CYP1A2 andUGT­glucuronidation

None

Clozapine 150 to 600 25­50 900 Tab, ODT, oralsuspension

12 CYP1A2, otherCYPs, and UGT­glucuronidation

CYP2D6(moderate)

Iloperidone 12 to 24 224

12 (CYP2D6Tab 18­26 CYP2D6 and

other CYPs toCYP3A4(moderate)

•

Δ

Δ

Δ

Δ

Δ

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poormetabolizeror receiving 2D6inhibitorcotreatment)

active andinactivemetabolites

Lurasidone 40 to 80 40

20 (renal orhepaticinsufficiency)

160

80 (moderate orsevere renalinsufficiency,moderatehepaticinsufficiency)

40 (severehepaticinsufficiency)

Tab 29­37 (steady state) CYP3A4 to activeand inactivemetabolites

None

Olanzapine 10 to 20 5 to 10 30 Tab, ODT, IM, LAI 30­38 CYP1A2 andUGT­glucuronidation

None

Paliperidone 6 to 12 6 12 ER tab, LAI 23 Paliperidone isexcreted mainlyunchanged inurinenecessitatingdose reduction inrenalinsufficiency

None

Quetiapine 150 to 750(immediaterelease)

400 to 800(extendedrelease)

50 750 (immediaterelease)

800 (extendedrelease)

Tab, ER tab 6­12 CYP3A4 None

Risperidone 2 to 6 1 to 2 8 Tab, ODT, LAI, oralsolution

20 CYP2D6 to active(paliperidone)and inactivemetabolites; P­gpsubstrate

CYP2D6(moderate)

Ziprasidone 40 to 160 40 to 80 200 Capsule, IM 7 oral

2­5 IM

CYP3A4 None

Doses shown are total daily dose, oral administration, for maintenance treatment of schizophrenia in otherwise healthy adults. For additionalinformation, refer to Lexicomp individual drug monographs included with UpToDate.

ODT: orally dissolving tablet; Tab: tablet; ER tab: extended­release tablet; IM: short­acting intramuscular injection; LAI: long­acting injectable (eg, depot); CYP:cytochrome P­450; P­gp: membrane P­glycoprotein transporters; UGT­glucuronidation: uridine 5'diphosphate­glucuronyltransferases* Usual maximum total oral daily dose for maintenance treatment of schizophrenia in adult patients without significant comorbidity. Doses shown may not be themaximum dose used in some clinical trials or in exceptional patients. • Only potent to moderate inhibitor effects are listed in this table. For additional information including moderate to weak inhibitor or inducer effects, and todetermine specific drug interactions, refer to individual drug monographs section on drug interactions and the Lexi­Interact program included with UpToDate.Δ Smoking may decrease blood concentrations of antipsychotics primarily metabolized by CYP1A2.

Prepared with data from:1. Lexicomp Online. Copyright © 1978­2014 Lexicomp, Inc. All Rights Reserved.2. Wynn GH, et al (eds) Clinical Manual of Drug Interaction Principles for Medical Practice APA publishing, Washington DC. Copyright © 2009.

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Antipsychotics for initial management of the acutely agitated adult patient with psychosis

Formulation RouteInitialdose(mg)

Frequency(hours)

Maximuminitialdose per24 hours(mg)

Time to peakplasma

concentration(hours)

Notes

First­generation agents

Haloperidol Short­actinglactate injection

IM, IV 2­5 0.5­2* 30 0.5­1 Sedation, hypotension and prolongationof QTc interval more pronounced withinjection. ↑ EPS risk.Oral solution PO 0.5­5 6 30 2

Droperidol Injection (short­acting)

IM, IV 2.5­5 2­4* 40 0.5 Rapid onset of 3­10 minutesadvantageous in severely agitatedviolent patients. Dose related QTcprolongation and risk of cardiacarrhythmias. ↑ EPS risk.

Fluphenazine Short­actinghydrochlorideinjection

IM 1.25 6 10 ND 1 mg short­acting IM injection isequivalent to ~2.5 mg oral. ↑ EPS risk.

Oral solution PO 1­2.5 6 10 3

Chlorpromazine Injection (short­acting)

IM, IV 25 1­4 200 0.5 Hypotension, sedation and injection sitepain are limiting side effects. Not a first­line agent.

Second­generation agents

Aripiprazole Injection (short­acting)

IM 9.75 2 30 1 Less sedating. Minimal prolongation ofQTc interval or orthostatic hypotension.

Disintegratingtablet, oralsolution

PO 10­15 2 30 3­5

Olanzapine Injection (short­acting)

IM 5­10 2­4 30 0.25­0.75 Decreased clearance in female and/ornon­smoking patients.

Disintegratingtablet

PO 5­10 0.5­2 20 5

Risperidone Disintegratingtablet, oralsolution

PO 1­2 0.5­2 4 1.5 Decreased clearance in renal and/orhepatic impairment.

Ziprasidone Short­actingmesylateinjection

IM 10­20 2­4 40 0.5­1 Dose related QTc prolongation and riskof cardiac arrhythmias.

Dose reduction necessary for older adults, debilitated patients and if used in combination with other sedation. See accompanying text fordiscussion of electrocardiograph and other monitoring for agents known to cause prolongation of the QTc interval.

ND: no data; EPS: extrapyramidal symptoms.* It may be necessary to repeat initial dose or fraction thereof after 15 to 20 minutes in patients with severe agitation until desired level of sedation attained.

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Disclosures: T. Scott Stroup, MD, MPH Other Financial Interest: Genentech [Schizophrenia (drug to treat negative/cognitive symptomsin schizophrenia not on market)]. Stephen Marder, MD Grant/Research/Clinical Trial Support: Novartis [Antipsychotic medications(iloperidone)]; Sunovion [Antipsychotic medications (lurasidone)]. Consultant/Advisory Boards: Pfizer [Antipsychotic medications(ziprasidone)]; Otsuka [Antipsychotic medications (aripiprazole)]; Lundbeck [Antipsychotic medications (aripiprazole)]. Murray B Stein,MD, MPH Nothing to disclose. Richard Hermann, MD Employee of UpToDate, Inc.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through amulti­level review process, and through requirements for references to be provided to support the content. Appropriately referencedcontent is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures