Schizophrenia and Bipolar Treatment Flashcards
Schizophrenia Treatment Goals
Decrease symptoms
Increase quality of life (minimize adverse effects from treatment, including weight gain, constipation, dyspepsia, diabetes, cardiac and EPS)
Encourage adherence
Decrease hospitalizations/health care costs (Schizophrenics utilize police and ED more than most)
Schizophrenia Treatment guidelines (General)
First Gens (Typicals):
>reduce positive symptoms equally at equivalent doses
>do not reduce negative symptoms well
>increased EPS, anticholinergic, sedation and hypotension
>less risk for meatbolic syndrome
Second Gens (Atypicals):
>reduce positive symptoms well
>moderate efficacy for negative symptoms
>possible effect on increasing cognition (Lurasidone at 5HT7 receptor)
>less EPS (5HT2 antagonism in nigrostriatal DA pathway)
>high risk for metabolic syndrome
Describe Metabolic Syndrome
Increased weight gain, increased BP, increased cholesterol, increased diabetes/insulin resistance
FGA Dosing Considerations
Potency thought to be related to D2 occupancy/affinity | Higher D2 affinity associated with stronger potency (generally 60% affinity to be effective, AEs seen at >80% affinity)
Dosed on ‘Chlorpromazine’ (CPZ) equivalents | Treatment responsive, multi-episode schizophrenia dosing should be in range of 300-1000 mg CPZ equivalents
Increased risk of EPS leads to decreased risk of ______________
Sedation
SGA Dosing Considerations
Consider and dose to side effects: Initial dosing should be low, titrate slowly to side effects
Maintenance dosing: Watch for long term side effects (metabolic syndrome, QT prolongation, Prolactin release, EPS)
Schizophrenia Algorithm
- 2nd Generation First
- Switch to a different 2nd Gen or to a 1st Gen
- Clozapine (only after 2 failed trials with other antipsychotics)
Schizophrenia Treatment Guidelines (TMAP)
First episode: SGA (risperidone, quetiapine, aripiprazole)
Acute severe psychosis (acute positive symptoms): Haldol (first gen with high potency, good for acute positive symptoms); Olanzapine (SGA with strong M and H1 receptor action, sedating)
Maintenance (usually life-long):
>Younger (SGA preferred, less sedating, less EPS)
>Middle age (SGA or FGA, more weight gain, diabetes risk)
>Treatment resistance (FGA or clozapine)
>Pregnant (Clozapine or Lurasidone, both Category B)
Special Considerations:
>Ziprasidone and Lurasidone must be taken with 350-500 cals of food
>the most common EPS with SGA is akathisia
>If cardiac concerns, avoid ziprasidone
>Risperidone doses over 6mg have heightened EPS risk
Schizophrenia Treatment Resistance Guidelines
After failed first drug, try a different SGA or FGA
After 2 failed trials, switch to Clozapine or an alternative SGA/FGA
Clozapine needs:
>weekly lab draws (WBC/ANC) and coordination between pharmacy and physician for dosing and lab draws
>REMS Clozapine Registry
>RPh do not dispense until next lab draw
Neutropenia and Luekopenia
Clozapine has high neutropenia/agranulocytosis risk
All FGA and SGA have risk of neutropenia (usually seen 4 weeks to 4 months of use; Haloperidol, olanzapine, quetiapine, risperidone)
Neutropenia defined as neutrophil cound below 1500/uL in whites and under 1200 for African/Middle Eastern
Leukopenia defined as white blood cell count under 4000/uL
Antipsychotic Adequate Trial
To classify as a non-responder you need to use an antipsychotic for at least 4-6 weeks (may need up to 12 weeks for Clozapine)
Assessing full 5effects of antipsychotics may take up to 12 weeks for all (up to 6 months for clozapine) –> meds can be switched sooner if there is acute relapse resulting in danger to themselves or to others
Antipsychotics risk of weight gain
Highest Risk: (SGA) olanzapine = clozapine)
Medium-High Risk: Low potency FGA
Medium Risk: Risperidone = Paliperidone = quetiapine
Medium-Low Risk: Medium potency FGA
Low Risk: High potency FGA = Aripiprazole = Ziprasidone
Diabetes/Insulin Resistance in antipsychotics
High Risk: (SGA) Colzapine, Olanzapine
Moderate RIsk: (SGA) Quetiapine, Risperidone
Lower Risk: Ziprasidone, Aripiprazole, FGAs
Should check HbA1c and blood glucose quartlerly when on SGAs
Prolactin Elevation Risk
Highest Risk: Risperidone = paliperidone = Haldol
High Risk: FGA
Medium-High Risk: Olanzapine
Medium Risk: Ziprasidone
Medium-Low Risk: Quetiapine = Clozapine
Low Risk: Aripiprazole
QT Prolongation Relative Risk
Highest Risk: Thioridazine, pimozide
High Risk: Ziprasidone > Paliperidone
Medium High Risk: Quetiapine = Risperidone = Olanzapine = Haloperidol
Medium Risk: Clozapine
Medium-Low Risk: Aripiprazole = Fluphenazine = Chlorpromazine
Clozapine Metabolism
Clozapine uses CYP1A2, 3A4 and 2D6 pathways for its metabolism
Cigarette smoking is a strong CYP1A2 inducer
75% of schizophrenic patients smoke
Caffeine also induces 1A2
*also a problem in olanzapine
Long-Acting AP injectables
Improve adherence to medication
Given in deltoid or glutes | Some pharmacists will administer
Very expensive | Some drug companies help pay or have assistance programs
If AEs present, there is no way to retrieve out of body
Always start with oral form first, then move to injectable
Medical Conditions which may precipitate mania
Stroke, Traumatic brain injury, Epilepsy, HIV/AIDS, Systemic Lupus Erythematosus (may not have bipolar disorder), Vitamin B12 deficiency, Cushing’s disease, Sleep deprivation, Light exposure, Extreme Stress, Wilson’s Disease
Drugs which may precipitate mania
Alcohol, bronchodilators, caffeine, cocaine, stimulants, steroids, tricyclic antidepressants, hallucinogens, dopamine agonists, pseudoephedrine, interferon
Bipolar DIsease (classification)
Bipolar 1 (classic bipolar disorder; both manic and depressive episodes of varying length)
Bipolar 2 (less severe manic episodes with similar bipolar episodes to Bipolar 1)
Cyclothymia (chronic but milder form of bipolar disorder; hypomania and depression that may last for years)
Mixed episodes (mania and depression occur simultaneously; individuals feel hopeless and depressed yet energetic and motivated to engage in risky behaviors)
Rapid cycling (four or more episodes of mania, depression or both within 1 year)
Bipolar Disorder Diagnosis
Destructive times for patients are either in Mania or Depressive phases of illness
Manic: at least 7 days when person has abnormally or persistently elevated or irritable mood; may alternate back and forth between elevated and irritable
Symptoms of manic episodes (DSM 5))
Inflated self-esteem or grandiosity (ranges from uncritical self-confidence to a delusional sense of expertise)
Decreased need for sleep
Intensified speech
Rapid jumping around of ideas or feels like thoughts are racing
Distractibility
Increase in goal-directed activity or psychomotor agitation (pacing, inability to sit still, pulling at skin or clothing)
Excessive involvement in pleasurable activities that have a high risk consequence
Hypomanic Symptoms (DSM 5)
Hypomanic episode is very similar to a manic one, but less intense
Only required to persist for 4 days and it should be observed by others that the person is noticeable different from his/her regular, non-depressed mood and that the change has an impact on his or her functioning
Bipolar Disorder 1 Treatment
Step 1: Lithium, VPA, or SGA (aripiprazole, quetiapine, olanzapine, paliperidone, risperidone, ziprasidone); Lithium OR VPA + SGA
Step 2: Switch agent with alternative (SGA, Li, or VPA); combine agents (Lithium, VPA or SGA - never 2 SGAs or clozapine)
Step 3: Combination (see above), CBZ, FGA or OXC
Step 4: ECT, adjunct with clozapine, Lithium + (VPA, CBZ or OXC) + SGA
Best Treatment Evidence for Mania
For euphoric hypomania/mania or psychotic mania (Lithium, valproate, aripiprazole, quetiapine, risperidone, or ziprasidone)
For dysphoric or mixed episodes (Divalproex, risperidone, aripiprazole, or ziprasidone)
Secondary options (CBZ - many drug interactions; Olanzapine - metabolic syndrome risk)
Combinations (lithium + VPA, Lithium + AAP (risperidone, quetiapine, olanzapine) ) OR (CBZ or oxcarbazepine + typical AP like haldol or perphenazine)
Don’t use ______________ by itself if patient has history of mania
Lamotrigine
Best evidence for Bipolar 2 or severe BPD1 with depression
If on lithium, add lamotrigine or quetiapine, then olanzapine with fluoxetine
If not on lithium, add Lamotrigine or QTP plus an antimanic (lithium, VPA or CPZ)
*make sure to watch out for VPA and Lamotrigine drug interactions
If not on Lithium and has not had a recent or severe manic episode, may try Lamotrigine by itself
May add on olanzapine or olanzapine with flu`oxetine
Antidepressants in bipolar disorder
Controversial | Not recommended as monotherapy due to mania switch | Not recommended in BPD 1 but may be appropriate in BPD 2 with mood stabilizer on board (lithium or lamotrigine) but evidence of improved stability is lacking
Suggested antidepressants are SSRI, SNRI (venlafaxine), MAOI (phenelzine)
*Avoid TCAs due to overdose potential
Later stages of Bipolar treatment or resistance
Oxcarbazepine (watch for hyponatremia)
Clozapine (treatment resistant cases only - for severe mania/mixed)
ECT (treatment resistant cases only - highly effective for acute mania)
Inhaled Loxapine (indicated to treat acute agitation in Bipolar 1)
Lithium
Indicated for acute mania and maintenance treatment in BPD 1 and 2
Serum levels 0.5-1.0 mEq/L
Prophylactic benefits are better for episodes or mania than for depression recurrence
Long term lithium treatment leads to a 5 fold decrease in suicide risk compared with placebo and other treatment Has neuroprotection (direct-illness modifying effect)
Lithium Adverse Effects
Cognitive dulling (memory impairment)
Tremor in hands | Slow information processing speed
Weight gain, Edema, Dermatitis
Polyuria in 70% and Diabetes Insipidus in 12-20%
Hypothyroidism (30% of long term patients) - causes breakthrough depression
Leukocytosis (increased WBC)
Pregnancy Category D (Cardiac malformations in trimester 1)
Lithium drug interactions
Should not be given with, or cautiously with:
NSAIDs (chronic or high intermittent use) increases Lithium
Ace inhibitors (Lisinopril, Enalapril) increase lithium
Thiazide diuretics (give with caution and with lowered lithium dose)
Na/Li balance required –> Too little Na will cause high Li
Haloperidol (encephalopathy has occured)
Lithium toxicity
Lithium level above 1.2, however, symptoms can appear within normal limits
GI upset, NVD, tremor, dystonia, hyperreflexia, ataxia, cardiac dysrhythmias
Neurotoxicity: confusion, stupor, decreased cognition, restlessness
Nephrotoxicity (dialysis required when Li levels greater than 4 mEq/L; Nephrogenic diabetes insipidus)
Dehydration can cause Li toxicity
Encephalopathy
Haldo + Lithium increase risk of neurological disorders, especially encephalopathy (other antipsychotics with Lithium have also been reported)
Symptoms: weakness, fever, tremors, lethargy, fluctuating cognition, delirium, ataxia, rigor in extremities, akinesia
EEG determiens neurological impairment
Stopping medications involved will usually reverse syndrome
Pharmacists role in lithium patient
Li low therapuetic index so get in this for lab levels (Labs will be reduced as patient takes Li for longer time)
Keep patient hydrated but avoid polydispia, take at bedtime with light snack if nausea, do not restrict sodium intake
Do not take with NSAIDs, COX2 inhibitors, ACEIs or diuretics without telling MD
May experience light hand tremor that may go away
Don’t stop taking med or interrupt treatment without MD
Notify MD if diarrhea, vomiting, unsteady GAIT, excessive urination, weak muscle onset, significant tremor, confusion, ataxia or slurred speech
Don’t start antidepressant without psychiatrist (No St. John’s wort, SAM-e, etc.)
Valproate
Valproic Acid IR TID
Divalproex (Depakote):
>Sprinkles DR on food
>DR BID
>ER Qd, less nausea, and 10-20% less bioequivalent doses
*DR 500 mg = ER 750 mg
>Therapeutic range is 50-125 mcg/L
>AEs: Sedation, nausea, vomiting, dizziness, in acutely manic patients
>Other AEs: Weight gain, reduced platelets and WBC, increased ammonia levels (encephalopathy in toxicity), alopecia in maintenance patients
Lamotrigine
Useful for Bipolar depression (limited anti-mania efficacy)
Often used with Lithium
Should not be used if history of severe or recent mania without antimanic on board
