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Antipsychotics for Schizophrenia

Antipsychotics for Schizophrenia

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Published by: psychopharmacology on Nov 03, 2012
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06/11/2015

Module 3 Indications Antipsychotics for Schizophrenia

Flavio Guzmán, MD

Outline
• Clinical aspects of schizophrenia relevant to pharmacological treatment • Acute phase
– Pre treatment assessment – Antipsychotic choice

• Refractory symptoms: assessment and management • Goals for maintenance phase

Psychosis & Schizophrenia
Antipsychotics are not specific for schizophrenia (“antischizophrenic”)
• Schizophrenia • Schizoaffective disorder • Mood disorders • Dementia • Personality disorders • Medical conditions

Psychotic symptoms

Janicak, P G., Marder S R., and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.

Schizophrenia has multiple psychopathological dimensions
Positive symptoms Negative symptoms Cognitive deficits Mood symptoms Other

• Delusions • Hallucinations • Thought disorder

• Apathy • Social withdrawal • Restricted affect • Anhedonia

• Attention • Memory • Executive function

• Dysphoria • Depression

• Agitation/ excitement

Janicak, P G., Marder S R., and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.

The “Ideal” treatment for schizophrenia

Positive symptoms

Negative symptoms
Based on:

Cognitive deficits

Gründer G, Hippius H, Carlsson A. The “atypicality” of antipsychotics: a concept re-examined and redefined. Nature Rev Drug Disc 8:197-202, 2009

FGAs improve positive symptoms
Effectiveness

Antipsychotics

Positive symptoms

Negative symptoms
Based on:

Cognitive deficits

Gründer G, Hippius H, Carlsson A. The “atypicality” of antipsychotics: a concept re-examined and redefined. Nature Rev Drug Disc 8:197-202, 2009

SGAs: effective for positive symptoms, less EPS
Effectiveness Variable efficacy

SGAs
Negative symptoms
Based on:

Positive symptoms

Cognitive deficits

Gründer G, Hippius H, Carlsson A. The “atypicality” of antipsychotics: a concept re-examined and redefined. Nature Rev Drug Disc 8:197-202, 2009

SGAs and cognition: the debate
Effective
-Some studies suggest that SGAs are superior to FGAs in improving cognition. - Effects are relatively weak compared to the severity of the impairments - CATIE trial (NIMH) showed no evidence of benefit of SGAs over FGAs in the treatment of cognitive symptoms

Not effective

Bilder RM, et al: Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Am J Psychiatry 159:1018–1028, 2002

Janicak, P G., S R. Marder, and M N. Pavuluri. Principles and Practice of Psychopharmacotherapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.

Secondary Negative Symptoms
Negative symptoms
Primary
Depression

Secondary
Extrapyramidal side effects
• • • Dose reduction Switch antipsychotic Anticholinergic drugs

Sadock, B J., V A. Sadock, and P Ruiz. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2009.

Key Points
• Antipsychotics (both FGAs and SGAs) are effective for positive symptoms of schizophrenia. • Antipsychotics are used in the management of acute episodes and in the prevention of relapses. • There is a need for more effective treatments for negative and cognitive symptoms.

Treatment phases
•First Episode Acute phase •Psychotic Relapse
Maintenance phase

Assessment

Assessment – Physical exam
• • • • Body mass index (BMI) Waist circumference Heart rate Blood pressure

Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Assessment – Neurological exam
• Signs of a movement disorder:
– Extrapyramidal symptoms (EPS): akathisia, parkinsonism, dystonias – Tardive dyskinesia
Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Assessment – Lab testing
• • • • • CBC Electrolytes Fasting glucose Lipid profile, Liver, renal and thyroid function tests • White blood cell (WBC) count with differential for patients treated with clozapine
Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Assessment - ECG
• History of cardiac disease • Antipsychotics:
– Clozapine – Thioridazine – Iloperidone – Ziprasidone
Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Acute Phase Management

Management of the acute episode
Tablets
• Patients might not swallow the tablet • Hepatic disease or slow GI absorption may increase the time required to attain steady-state concentrations

Liquid concentrates
Orally-dissolving formulations Short acting parenteral preparations
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008

Short-acting parenteral preparations
Advantages Disadvantages

• Useful in acute • Risk of injury to the agitation patient and the caregiver • Bypass first-pass metabolism in the liver • High doses of highand gut potency drugs can lead to dystonia or akathisia
Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008

Treatment Course
Clinical Improvement of Psychotic Symptoms

2 weeks

4 weeks

Months

Based on: Agid O, Kapur S, Arenovich T, Zipursky RB. Delayed-onset hypothesis of antipsychotic action: a hypothesis tested and rejected. Archives of general psychiatry 2003;60:1228-35

Antipsychotic choice
Previous response

Adverse effects profile • EPS: high potency FGAs (haloperidol) • Weight gain and metabolic effects: olanzapine, clozapine • Hyperprolactinemia: FGAs, risperidone, paliperidone
Janicak, P G., Marder S R., and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.

Key Points
• A pretreatment assessment is recommended, although in some situations it may be difficult to implement. • Patients show most of the clinical response in the first 4 to 6 weeks of treatment. • Antipsychotic choice is often guided by previous response to treatment and adverse effects profile.

Refractory Symptoms
• Assessment • Management

Assessing refractory symptoms in schizophrenia
Check adherence to treatment Check adequacy of time and dose

Review diagnosis

Consider other causes of non-response • Comorbid substance misuse • Physical illness
National Institute for Health and Clinical Excellence (2011) [Schizophrenia]. [CG82].

Management of Refractory Symptoms
Dose increase Switch AP Add a second AP Switch to clozapine
Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Changing to another antipsychotic
• Because of:
– Lack of effectiveness – Adverse effects

• Can be helpful when a poor response is related to side effects. • Less beneficial when the initial medication lacked effectiveness.
Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Switching antipsychotics
Standard cross-titration

Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Medication changes
Higher relapse risk

Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Adding a second antipsychotic
• Common practice. • Little evidence supporting the use of two antipsychotics. • Some randomized trials indicated that augmentation of clozapine with another antipsychotic may have some benefit.
Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Changing to clozapine
• For patients who experience persistent and clinically significant positive symptoms of schizophrenia after trials of two other antipsychotic medications. • Clozapine reduced suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide. • Can cause severe a life threatening side effect: agranulocytosis.
Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/

Key Points
• When assessing refractory symptoms check adherence to treatment, review diagnosis and consider other causes of non-response. • There is little evidence for combining two antipsychotics. • Clozapine can be used after two trials with other antipsychotics.

Maintenance Phase
Preserve symptom remission Prevent psychotic relapse Implement a plan for rehabilitation

Optimize functioning

Improve quality of life

American Psychiatric Association ( 2004 ) Practice guideline for the treatment of patients with schizophrenia, 2nd edition . American Psychiatric Publishing, Inc , Washington DC, USA, 1–184

References
• • • • • • American Psychiatric Association ( 2004 ) Practice guideline for the treatment of patients with schizophrenia, 2nd edition . American Psychiatric Publishing, Inc , Washington DC, USA, 1–184 Janicak, P G., Marder S R., and. Pavuluri M N. Principles and Practice of Psychopharmacotherapy. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010. National Institute for Health and Clinical Excellence (2011) [Schizophrenia]. [CG82]. Sadock, B J., V A. Sadock, and P Ruiz. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2009. Stroup, S., Marder S. (2012). Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. UpToDate. Retrieved from http://www.uptodate.com/ Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008

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