PHARMACOLOGICAL GUIDELINES IN THE

TREATMENT OF SCHIZOPHRENIA

BY. EHAB ELBAZ16-12-2012

REFERNCES► Thomas RE Barnes and the Schizophrenia Thomas RE Barnes and the Schizophrenia

Consensus Group of the British Association for Consensus Group of the British Association for Psychopharmacology Psychopharmacology (2011)(2011) : : Evidence-based Evidence-based guidelines for the pharmacological treatment of guidelines for the pharmacological treatment of schizophrenia: recommendations from the British schizophrenia: recommendations from the British Association for PsychopharmacologyAssociation for Psychopharmacology . Journal of . Journal of Psychopharmacology.25(5) 567Psychopharmacology.25(5) 567––620620

► David Taylor, Carol Paton and Shitij Kapur David Taylor, Carol Paton and Shitij Kapur (2009)(2009) : :The South London and Maudsley NHS The South London and Maudsley NHS Foundation Trust & Oxleas NHS Foundation Trust Foundation Trust & Oxleas NHS Foundation Trust PRESCRIBING GUIDELINESPRESCRIBING GUIDELINES . Informa healthcare . . Informa healthcare . LondonLondon

OBJECTIVES1.1. Step by stepStep by step approach for drug approach for drug

treatment of schizophrenia in treatment of schizophrenia in different stages of the illness.different stages of the illness.

2.2. Develop Develop one styleone style of prescription that of prescription that is evidence based.is evidence based.

3.3. Minimize Minimize faultyfaulty prescription as prescription as possible.possible.

Q :Q : What are the phases of What are the phases of

treatment of schizophrenia as treatment of schizophrenia as a chronic disease ?a chronic disease ?

1.1. ProdromaProdroma2.2. First episode psychosisFirst episode psychosis3.3. Maintenance and relapse preventionMaintenance and relapse prevention4.4. Relapse or acute exacerbationRelapse or acute exacerbation

Q:Q: Can we recognize the Can we recognize the prodromal phase of prodromal phase of schizophrenia ?schizophrenia ?

► The term The term ‘‘At-risk Mental StateAt-risk Mental State’’ or or ‘‘Ultra High Ultra High RiskRisk’’ is more appropriate than is more appropriate than ‘‘prodromeprodrome’’, as , as the majority of subjects will not progress to the majority of subjects will not progress to a major psychotic disorder.a major psychotic disorder.

► Attenuated positive symptoms, major Attenuated positive symptoms, major recent decline in function in someone who recent decline in function in someone who has a schi-zotypal personality disorder, or a has a schi-zotypal personality disorder, or a family history of psychosis.family history of psychosis.

► Subjective disturbances in thinking, Subjective disturbances in thinking, language and attention language and attention

► High risk (20High risk (20––40%) of progression to frank 40%) of progression to frank psychosis within 2 yearspsychosis within 2 years

Q: Q: Is there any thing that can Is there any thing that can be done in this prodromal be done in this prodromal phase ?phase ?

►Encourage a therapeutic relationshipEncourage a therapeutic relationship► Assess the nature and impact of any Assess the nature and impact of any

substance usesubstance use► If antipsychotic medication is If antipsychotic medication is

considered should be treated as off-considered should be treated as off-label , short-term, Very low doses .label , short-term, Very low doses .

► Individual CBT can be considered.Individual CBT can be considered.

Q:Q: In an established first In an established first episode schizophrenia ,how episode schizophrenia ,how to proceed ?to proceed ?

Q: Q: In case of relapse or acute In case of relapse or acute exacerbation , what to do ?exacerbation , what to do ?

Recommendations regarding medication adherence

► Offer a choice of medication . Take into account the known adverse effect Offer a choice of medication . Take into account the known adverse effect profiles of individual antipsychotics, a patientprofiles of individual antipsychotics, a patient ’’s past experience of adverse s past experience of adverse effects, and the risk of drug interactions and past medical history. effects, and the risk of drug interactions and past medical history.

► The regimen should be as simple as possible (number of tablets and the The regimen should be as simple as possible (number of tablets and the number of times each day). number of times each day).

► Asking the patients at regular intervals how much of their medication they Asking the patients at regular intervals how much of their medication they have taken in the last week, and their view regarding the efficacy of this have taken in the last week, and their view regarding the efficacy of this medication.medication.

► Using one of the rating scales or checklists to assess a patientUsing one of the rating scales or checklists to assess a patient ’’s attitudes s attitudes towards medication. towards medication.

► In patients with a history of non-adherence leading to relapse, consideration In patients with a history of non-adherence leading to relapse, consideration should be given to using more objective methods to monitor adherence to oral should be given to using more objective methods to monitor adherence to oral medication regimens such as pill counts or plasma drug levels. medication regimens such as pill counts or plasma drug levels.

► A depot/long-acting injection formulation should be considered when this is A depot/long-acting injection formulation should be considered when this is preferred by the patient, previous non-adherence has led to frequent relapse preferred by the patient, previous non-adherence has led to frequent relapse or the avoidance of non-adherence is a clinical priority. or the avoidance of non-adherence is a clinical priority.

Q : Q : My patient can not tolerate the My patient can not tolerate the

antipsychotic because of its antipsychotic because of its side effect , and I want to side effect , and I want to change it , what drug do I change it , what drug do I choose?choose?

Q: Q: How to prevent relapse of How to prevent relapse of schizophrenia ?schizophrenia ?

Recommendations for maintaining response and

relapse prevention► continued maintenance with doses of antipsychotic continued maintenance with doses of antipsychotic

medication within the recommended range for 1-2 years in medication within the recommended range for 1-2 years in first episode and in subsequent episodes the treatment is first episode and in subsequent episodes the treatment is indefinite .indefinite .

► Before undertaking a switch in antipsychotic medication, an Before undertaking a switch in antipsychotic medication, an adequate trial is to be conducted in terms of dosage, duration adequate trial is to be conducted in terms of dosage, duration and adherence.and adherence.

► The care plan should address reversible risk factors for The care plan should address reversible risk factors for

relapse, such as comorbid substance use, poor adherence and relapse, such as comorbid substance use, poor adherence and a critical environment.a critical environment.

► Depot formulations should be considered when adherence is a Depot formulations should be considered when adherence is a priority and where a patient expresses a preference for such a priority and where a patient expresses a preference for such a formulation. formulation.

Q: Q: Patients with predominantly Patients with predominantly negative symptoms donnegative symptoms don’’t t respond well , is there any respond well , is there any thing more that can be thing more that can be done ?done ?

► Negative symptoms may be 1ry or Negative symptoms may be 1ry or 2ry.2ry.

► 1ry _______ predict poor outcome.1ry _______ predict poor outcome.► 2ry _______ ( depression , 2ry _______ ( depression ,

bradykinesia, social withdrawal )bradykinesia, social withdrawal )

Recommendations for the Recommendations for the pharmacologicalpharmacological

management of negative symptomsmanagement of negative symptoms► Early identification and treatment of Early identification and treatment of

psychosis .psychosis .► Chose antipsychotic that give balance Chose antipsychotic that give balance

between efficacy and side effect.between efficacy and side effect.► Ensure EPS and depression are detected and Ensure EPS and depression are detected and

treated if present.treated if present.► Consider augmentation of antipsychotic with Consider augmentation of antipsychotic with

an antidepressant .an antidepressant .► If clozapine is prescribed, consider If clozapine is prescribed, consider

augmenting with lamotrigine or a suitable augmenting with lamotrigine or a suitable second antipsychotic. second antipsychotic.

Q : Q :

What about combined What about combined antipsychotics ?antipsychotics ?

► Antipsychotic polypharmacy is a Antipsychotic polypharmacy is a widespread practice.widespread practice.

► Substantial evidence suggest that Substantial evidence suggest that polypharmacy is harmful.polypharmacy is harmful.

► Very limited evidence supports the efficacy Very limited evidence supports the efficacy of combined antipsychotics.of combined antipsychotics.

► Q: Q: My patient has treatment resistant My patient has treatment resistant

schizophrenia and I started clozapine schizophrenia and I started clozapine therapy but the outcome is therapy but the outcome is unsatisfactory , what is the next unsatisfactory , what is the next move ? move ?

Q: Q:

What to do if clozapine is What to do if clozapine is not an option ?not an option ?

Q : Q :

What is the role of ECT in What is the role of ECT in schizophrenia ?schizophrenia ?

► Reviewing the literature by Haskett and Loo Reviewing the literature by Haskett and Loo (2010) : the combination of ECT and (2010) : the combination of ECT and antipsychotic medication may be a useful antipsychotic medication may be a useful option for patients with schizophrenia that has option for patients with schizophrenia that has proved unresponsive to pharmacological proved unresponsive to pharmacological interventions.interventions.

► ECT combined with antipsychotic medications ECT combined with antipsychotic medications was an option to be considered when the was an option to be considered when the treatment aim was rapid global improvement treatment aim was rapid global improvement and symptomatic reduction, and for patients and symptomatic reduction, and for patients whose illnesses had shown only a limited whose illnesses had shown only a limited response to medication alone. response to medication alone.

IN BRIEFIN BRIEFSchizophrenia + pregnancy ______Schizophrenia + pregnancy ______

►Chloropromazine Chloropromazine

►Halpridole Halpridole

IN BRIEFIN BRIEFSchizophrenia + breast feeding ________Schizophrenia + breast feeding ________

►Sulpiride Sulpiride

►Olanzapine Olanzapine

IN BRIEFIN BRIEFAntipsychotics in renal impairmentAntipsychotics in renal impairment : :

►first-generation antipsychotic first-generation antipsychotic –– suggest haloperidol 2suggest haloperidol 2––6 mg a day 6 mg a day

►second-generation antipsychotic second-generation antipsychotic –– suggest olanzapine 5 mg a daysuggest olanzapine 5 mg a day

IN BRIEFIN BRIEFAntipsychotics in hepatic impairment :Antipsychotics in hepatic impairment :

► Haloperidol : low dose Haloperidol : low dose ► Sulpiride/amisulpride : Sulpiride/amisulpride : no dosage no dosage

reduction required if renal function is normalreduction required if renal function is normal