Schizoaffective Disorder Hannah Allegretto University of Pittsburgh School of Pharmacy PharmD Candidate 2013

The Case: ES is a 30yo male presenting to the ER on 5/10/2012 due to worsening psychosis ▫Patient was on depakote, discontinued due to toxicity Patient was very anxious, pacing back and forth, and was becoming agitated. Patient admitted to racing thoughts and auditory hallucinations

The Case: Past Medical History ▫Axis I: Schizoaffective disorder ▫Axis II: Deferred ▫Axis III: EPS, seizure disorder, elevated blood ammonia secondary to depakote ▫Axis IV: Antisocial behavior

Schizoaffective Disorder: An Overview Chronic and disabling mental disorder Accounts for one-fourth to one-third of all schizophrenic patients Characterized by a combination of schizophrenic symptoms along with a mood disorder May be distinguished from a mood disorder by the fact that delusions/hallucinations must be present for at least two weeks in the absence of prominent mood symptoms.

Symptoms Changes in appetite/energy Disorganized speech Lack of hygiene/grooming Sleep disturbance Social isolation Concentration problems Paranoia Delusions of reference Hallucinations

Diagnostic Criteria: Schizoaffective Disorder An uninterrupted period of illness during which there is either a Major Depressive Episode, a Manic Episode, or a Mixed Episode concurrent with symptoms that meet Criterion A for Schizophrenia. ▫Criterion A: Two (or more) of the following, each present for a significant portion of time during a 1- month period (or less if successfully treated):  Delusions  Hallucinations  Disorganized speech  Grossly disorganized or catatonic behavior  Negative symptoms

Diagnostic Criteria: Schizoaffective Disorder Delusions/hallucinations for at least 2 weeks in the absence of prominent mood symptoms Symptoms meeting criteria for a mood episode present for substantial portion of the total duration of active/residuals periods of illness Disturbance not due to direct effects of a substance (drugs/medicine) or a general medical condition

Schizoaffective Disorder Subtypes Two types: ▫Bipolar type:  Disturbance includes manic or mixed episode  Disturbance includes a manic or mixed and major depressive episode ▫Depressive type:  Disturbance only includes a major depressive episode

Treatment Combination of drug therapy and psychosocial interventions Individualized to the patient ▫often requires trial and error method Antipsychotic medications ▫Treat the symptoms of psychosis Mood stabilizers/Antidepressants ▫Mood stabilizers for bipolar type ▫Antidepressants for depressive type Medication Adherence crucial ▫Non-adherence is greatest predictor of relapse

Treatment Antipsychotics ▫2 nd Generations (SGAs):  1 st line treatment against schizophrenia  Also known as “atypical antipsychotics”  Produce an antipsychotic response without causing extrapyramidal symptoms  Advantages:  Enhanced efficacy  negative symptoms and cognition  (Near) absence of tardive dyskinesia  Lack of effect on serum prolactin

SGAs Clozapine (Clozaril) Risperidone (Risperdal) Olanzapine (Zyprexa) Quetiapine (Seroquel) Ziprasidone (Geodon) Aripiprazole (Abilify) Paliperidone (Invega)* Asenapine (Saprhis) Iloperidone (Fanapt) Lurasidone (Latuda) Long-Acting Injectable SGAs Risperidone (Risperdal Consta) Paliperidone palmitate (Invega Sustenna) Olanzapine pamoate (Zyprexa Relprevv) *Paliperidone is the only antipsychotic FDA approved for schizoaffective disorder

SGAs Greater affinity for 5-HT than D2 ▫Also work on histamine, muscarinic, and alpha 1 and 2 receptors Less movement disorders than with FGAs Metabolic effects are prevalent ▫Olanzapine and clozapine hold greatest risk

First Generation Antipsychotics (FGAs) D 2 blockade of >60% needed in the mesolimbic pathway for antipsychotic effect ▫>80% Blockade of D 2 receptors  higher risk of EPS Work to reduce positive symptoms ▫Delusions, hallucinations, disorganized speech, psychomotor agitation Side Effects: ▫EPS, increased prolactin levels

FGAs Haloperidol (Haldol) Fluphenazine (Prolixin) Perphenazine (Trilafon) Thioridazine (Mellaril) Chlorpromazine (Thorazine) Thiothixene (Navane) Trifluoperzine (Stelazine) Loxapine (Loxitane)

Treatment Algorithm

Mood Stabilizers Lithium ▫Used to treat manic episodes in bipolar disorder ▫Alters sodium transport in nerve and muscle cells ▫Therapeutic level for bipolar disorder: mEq/L ▫Toxicity induced by ACE-I, NSAIDS, diuretics

Mood Stabilizers Anticonvulsants: ▫Divalproex:  Indicated for manic bipolar disorder  MOA unknown, but may be attributed to increased GABA in the brain  Can cause hyperammonemia, dose related thrombocytopenia ▫Carbamazepine:  Inhibits voltage dependent sodium channels  Major substrate of CYP 3A4; numerous DDIs

Mood Stabilizers Anticonvulsants ▫Lamotrigine  Indicated for the treatment of bipolar I disorder  In patients not on enzyme-inducing drugs or on valproic acid  Inhibits sodium and voltage gated calcium channels  Advantage: once daily dosing  In females with oral contraceptive use, blood levels of lamotrigine will be DECREASED

Antidepressants Mainly used in the depressive subtype May help improve negative symptoms Selective-Serotonin Reuptake Inhibitors (SSRIs) are preferred ▫Less adverse effects than other classes Currently available SSRIs: ▫Citalopram ▫Escitalopram ▫Fluoxetine ▫Fluvoxamine ▫Sertraline ▫Paroxetine

The case: Current Medications: ▫Acetaminophen 650mg PO q4h PRN ▫Benztropine 1mg PO TID ▫Carbamazepine XR 600mg PO 8AM, 800mg PO QPM ▫Clonazepam 1mg PO daily, 2mg PO HS ▫Docusate 100mg PO BID ▫Haloperidol 2mg PO or IM q4h PRN ▫Lorazepam 1mg PO or IM q4h PRN ▫Olanzapine 30mg PO HS ▫Thiothixene 10mg qAM, 15mg PO HS

The case: Patient has failed treatment previously on the following: ▫Invega ▫Clozapine ▫Valproic Acid ▫Lithium Patient is candidate for combination therapy and ECT ▫Currently refusing ECT therapy, although helpful in past

Electroconvulsive Therapy Electric currents pass through the brain  intentionally triggers a seizure ▫Brain chemistry is altered, often helping with many mental illnesses Negative stigma attached due to older practices ▫Now, ECT much more structured  patients under anesthesia during procedure Benefits many mental disorders ▫Severe/Treatment-resistant depression ▫Severe mania ▫Catatonia ▫Agitation/aggression in dementia patients

Patient Progress Patient remains isolative on unit, limited interaction with staff Patient repeatedly taps his leg, and seems to be responding to internal stimuli Denies suicidal/homicidal ideations Currently refuses ECT, even though was beneficial in past

The case: Plan: ▫Schizoaffective disorder:  Continue olanzapine 30mg PO HS  Continue thiothixene 10mg PO qAM, 15mg po qHS  Initiate process for court ordered ECT if patient still refusing treatment  Continue benztropine 1mg PO TID  Continue clonazepam 1mg PO daily, 2mg PO HS and lorazepam 1mg PO/IM q4h PRN  Continue haloperidol 2mg PO/IM q4H PRN

The case: Plan: ▫Mood Symptoms within Schizoaffective Disorder/Seizure Prophylaxis  Continue Carbamazepine XR 600mg PO qAM, 800mg PO qPM ▫Psychosocial Therapy:  Standard of Care  Antipsychotics can help with the symptoms, but social adjustment and competitive employment still an issue  Cognitive Behavioral Therapy (CBT) promising

CBT Goals: ▫Reduce intensity of delusions/hallucinations ▫Promote active participation of patient in reducing relapse risk and disability Techniques: ▫Exploring the nature of the hallucinations/delusions ▫Challenging the validity of symptoms ▫Reality Testing

Conclusion Schizoaffective disorder is chronic and disabling May require a combination of both medications and nonpharmacologic therapy ▫CBT/ECT Every patient is different. ▫Must individualize treatment based on responses Medication adherence is crucial ▫Greatest predictor of relapse

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