Psychotic Disorders Flashcards
Abbreviations
- FGA: First generation antipsychotics (typicals)
- SGA: Second generation antipsychotics (atypicals)
- 5HT: serotonin
- DA: dopamine
- NE: norepinephrine
Psychosis
- Mental disorder with severe loss of contact with reality
- Delusions, hallucinations, disorganized speech, erratic behaviors
- Difficult to recognize what is real and what isn’t
Schizophrenia Characteristics
- Disturbance in expected or prior level of functioning in one or more major areas (work, relationships, etc)
- Active symptoms persist for at least one month and residual for at least 6 months
- Symptoms aren’t consistent with other diagnosis
- Not attributable to substance use or another medical condition
Schizophrenia Presentation
2+ symptoms persist good portion of a month:
- Delusions*
- Hallucinations*
- Disorganized speech*
- Grossly disorganized or catatonic behavior
- Negative symptoms
One of the symptoms must be one of the *
Schizoaffective Disorder
- Presence of a major mood episode (mania, depression) concurrently with schizophrenia symptoms
- Presence of delusions or hallucination for 2+ weeks in the absence of a major mood episode during lifetime of illness
- Simply, SCZ + Mood disorder
Secondary Psychotic Disorders
- Collective term encompassing psychotic symptoms caused by another medical condition or substance
- Substance-induced psychosis can occur during active exposure/intoxication or the subsequent withdrawal
- Symptoms cannot occur exclusively in the context of delirium or another cognitive disorder
- Delirium fluctuates throughout the day
Positive Symptoms
- Hallucination
- Delusions
Negative Symptoms
- Anhedonia
- Amotivation
- Social withdrawal
- Flat affect
Cognitive Symptoms
- Poor short/long-term memory
- Speech/communication difficulties
- Inattention
APA Goals of Therapy
- Reduce/eliminate symptoms
- Maximize QoL and adaptive functioning
- Promote/maintain recovery from the debilitating effects of illness to the max extent possible
Acute Treatment Goals
- Ensure safety of all involved
- Reduce agitation, aggression, hostility
- Relieve detrimental effects of hallucinations (anxiety)
Chronic Treatment Goals
- Maintain control of symptoms
- Improve social functioning/community integration
- Maintain safe and stable living environment
- Treat and rehabilitate substance abuse
- Educate and involve caregivers
- Manage chronic comorbidities
- Minimize medication side effects
High Potency FGAs (EX/Characteristics)
- Strong D2 antagonism
- Weaker alpha-antagonism
- Minimal anticholinergic effects
- Minimal 5HT2A antagonism (little/no effect on treating negative symptoms)
- EX: Haloperidol, fluphenazine, perphenazine
Low Potency FGAs (EX/Characteristics)
- Less strong D2 antagonism
- High alpha-antagonism
- Strong anticholinergic effects
- Minimal 5HT2A antagonism (little/no effect on treating negative symptoms)
- EX: Chlorpromazine
SGAs
- Characterized by higher affinity 5HT2A affinity than D2
- More varied receptor pharmacology than FGAs
- Significant difference in AEs between the classes
- Similar efficacy to FGAs for positive symptoms, possible better efficacy for negative symptoms
EPS
Extrapyramidal Symptoms:
- Akathisia
- Pseudoparkinsonism
- Acute dystonia
- Tardive dyskinesia
Akathisia
- Unknown mechanism
- Feeling of internal restlessness and anxiety
- High incidence with all antipsychotics, FGA»_space; SGA
- Onset: days to weeks
- Risk factors: high potency FGAs, high doses, rapid dose escalation**
- Treatment: lower dose or change to low-potency, lipophilic B-blockers, mirtazapine, trazodone, benzos
Pseudoparkinsonism
- Mechanism: Excessive DA blockage in the nigrostriatal pathway
- High incidence with FGAs
- Onset: 1 to 3 months
- Risk factors: high-potency FGAs, high dose, >40 y.o., female
- Treatment: lower dose or change to low potency, short-term anticholinergics (benztropine, diphenhydramine)
- Avoid chronic anticholinergic use. negative cognitive effects
Acute Dystonia
- Mechanism: Excessive DA blockage in the nigrostriatal pathway
- Occurs in 2-10% of FGA patients
- Onset: within 3 days in most cases
- Risk factors: High potency FGAs, high doses, history of dystonias, male, younger age, intramuscular or IV administration*
- Treatment: stat intramuscular anticholinergics => benzos (Diphenhydramine, bentropine, or lorazepam)
Tardive Dyskinesia (TD)
- Mechanism: Induced D2 receptor hypersensitivity
- Involuntary, repetitive, potentially irreversible, abnormal movements
- Onset: months to years
- Risk factors: older age, dose/duration, affective disorder, med non-adherence, use of anticholinergics
- Treatment: change therapy (works 1/2 the time), clozapine or quetiapine are preferred alternatives
QTc Prolongation
- Leads to Torsades de pointes => V. fib => sudden cardiac death
- Dose dependent effect seen to varying degree with most FGAs/SGAs (Exclusion: aripiprazole, lurasidone)
- Worst offenders: thioridazine, ziprasidone
- Prevention: Baseline and ECG follow-up, avoid high risk agents if baseline QTc > 450 msec, D/C therapy if QTc > 500 msec
Hyperprolactinemia
- Most prominent with FGAs, risperidone, and paliperidone
- Symptoms in women: amenorrhea, sexual dysfunction, decreased BMD
- Symptoms in men: breast pain, gynecomastia, sexual dysfunction, decreased BMD
- Treatment (only if symptomatic): change antipsychotic (aripiprazole), metformin may reverse amenorrhea, estrogen/progestin/testosterone/bisphosphonate for decreased BMD
Metabolic Complications
- Required in label warnings for all SGAs
- Higher prevalence of smoking, sedentary lifestyle, poor nutritional habits put SCZ patients at a higher risk
- Higher baseline rates of diabetes and CV mortality than normal (twice)
- Increased weight, fasting lipids, mean fasting/post-load blood glucose, and possible mortality all associated with SGAs
- Highest risk: clozapine, olanzapine
Metabolic Complication Treatment
- Diet and exercise
- Metformin: reduces weight gain from antipsychotics
- Statin therapy if indicated based on ASCVD score
- Other options have minimal effect
Acute Control of Psychotic Agitation
- Provide seclusion with minimal sensory stimulation
- Avoid use of physical restraints unless combative
- Always attempt oral medications first to reduce risk of staff harm from forced IM administration
- Place on direct observation
- Usually use antipsychotic, benzo, and anticholinergic concurrently
- 5-2-1: 5 mg haloperidol + 2 mg lorazepam + 1 mg benztropine
- B52: 50 mg diphenhydramine + 5 mg haloperidol + 2 mg lorazepam
- Olanzapine and ziprasidone are also options
Olanzapine + Benzo Interaction
- Not recommended due to excessive sedation and cardiorespiratory depression
- IM olanzapine/parenteral benzo specifically
- Avoid coadministration within one hour of each other
APA SCZ Guidelines
- Treat with an antipsychotic and monitor for effectiveness and SE
- Treatment-resistant SCZ should be treatment with clozapine (2 antipsychotics at appropriate doses for at least 6 weeks)
- Treat with clozapine if suicidal thoughts/ideation or aggressive behavior remains substantial even after treatments
Texas Medication Algorithm
- Stage 1: Single SGA
- Stage 2: Different SGA or FGA
- Stage 3: Clozapine
- Stage 4: Add SGA/FGA or ECT to clozapine
- Stage 5: Try a single SGA or FGA that hasn’t been tried
- Stage 6: Combine any of the above options
First Episode Psychosis
- Use a team-based, multimodal approach to treatment
- Consider a SGA
- Try using lower doses
Other Special Consideration
- Clozapine: Comorbid Parkinsons, development of TD
- ECT: Failure of clozapine, catatonia, persistent suicidality
- Long-acting injectables: repeated medication non-adherence
Long-Acting Injectable Basics
- IM injections administered in addition or in place of oral
- Formulation for prolonged absorption that lasts weeks
- Exhibit absorption-dependent kinetics
- Must verify effects and tolerability with oral agents first
Long-Acting Injectable Benefits
- Guaranteed medication adherence (theoretically)
- Possibly reduced relapse and readmission notes
- Impossible for patient to intentional overdose
- Facilitates routine outpatient follow-up
Long-Acting Injectable Drawbacks
- Potentially painful
- Require relatively frequent clinic visits
- Negative stigma
- Limited ability to titrate or adjust dose
- Expensive
Haloperidol Decanoate
- FGA LAI
- Dose: 50-200 mg every 2-4 weeks
- 10x PO dose = IM Dose
- Loading strategies for IM/PO dosing
- Formulated in sesame oil, caution with allergies
Fluphenazine Decanoate
- FGA LAI
- Dose: 12.5-50 mg every 2-4 weeks
- 1.25x PO dose (daily) = IM dose (every 3 weeks)
- No loading strategy
- Overlap PO therapy by 2-6 weeks
- Formulated in sesame oil, caution with allergies
Risperidone
- Risperdal Consta
- SGA LAI
- Dose: 12.5-50 mg every 2 weeks
- Start IM doses at 25 mg and adjust PRN
- No loading strategy
- Oral bridge of 3 weeks minimally
- Adjustment needed for renal and hepatic impairment
Perseris
- New LAI form of risperidone approved in 2018
- First SQ LAI approved
- Dose: 90-120 mg every 4 weeks
- No oral bridge needed
- 3 mg PO => 90 mg SQ, 4 mg PO => 120 mg SQ
Invega Sustenna
- Paliperidone
- SGA LAI
- Dose: 39-234 mg IM every 4 weeks
- 12 mg PO daily = 234 IM monthly (same for 6 mg risperidone)
- Loading strategy
- No PO overlap
- Need to adjust for renal impairment (CrCl < 80)
Invega Trinza
- Paliperidone
- First and only 3 month (SGA) LAI
- Patient must be on Invega Sustenna for at least 4 months prior to switch to Trinza
- No loading strategy or oral bridge
- Make dose adjustment to Sustenna before transitioning
Aripiprazole
- Abilify Maintena
- SGA LAI
- Dose: 400 mg every 4 weeks
- Lower to 300 mg if AE occur
- No strong PO to IM conversion data
- No loading strategy
- Oral bridge: 2 weeks (10-20 mg daily)
Aripiprazole Lauroxil
- Aristada
- SGA LAI
- Dose: 441mg, 662mg q 4 weeks, 882mg q 4-6 weeks, or 1064mg q 8 weeks
- More complicated PO to IM conversion
- Loading strategy
- Needs a 3 week oral bridge without Initio administation
- Dose adjust when used with CYP3A4/2D6 inhibitors/inducers
- Maintena is more reliable PK/conversion wise
Olanzapine
- Zyprexa Relprevv
- SGA LAI
- Black box: Post-injection delirium/sedation syndrome (PDSS)
- REMS criteria to be prescribed and used
- Must go to a facility for administration, be observed for at least 3 hours, and have transport home after each injection