Psychiatric disorders Flashcards
What are the major psychiatric disorders we will be focusing on
Bipolar disorder
Schizophrenia
Life time prevalence of schizophrenia in the US
1%
Lifetime prevalence of suicide among schizophrenic patients
10%
Genetic risks of schizophrenia
3% if 2nd degree relative has it
10% if first degree relative has it
40% if both parents have it
Mono-zygotic twin risk 48%
Presentation of schizophrenia
NOT split personality
Chronic diagnosis of thought and affect
Acute schizophrenic psychotic episodes
Auditory hallucinations (especially voices) Delusions (fixed false beliefs) Ideas of influence (outside forces control their actions)
Positive schizophrenic symtoms
Most obvious/dramatic
Suspiciousness, unusual thought content, hallucinations, etc.
Negative schizophrenic sx
Functional impairments
Affect flattening, alogia, anhedonia
Cognitive schizophrenic sx
Impaired attention, working memory, executive function
Schizophrenia tx overview
Pharmacotherapy = mainstay
Nonpharmacological tx for schizophrenia
Psychosocial rehab = mainstay
What measurements should you be looking at when getting ready to start treatment for schizophrenia to establish a baseline?
**Doing so to rule out medical or substance abuse causes** Vitals EKG CBC (fasting glucose) Electrolytes Lipid studies LFTs Thyroid functions Renal fx Urine drug screen
Original rationale for pharmacotherapy of schizophrenia
Acute psychotic episodes increase DA neurotransmission
Results in hypersensitivity to stimuli
(this is the original dopamine hypothesis)
Current rationale for pharmacotherapy of schizophrenia
Since inhibitory neurons are modulated by DA 5-HT, Ach and NE, these become targets for new Aps
Newer dysregulation hypothesis
Neurochemistry associated with schizophrenia
AP efficacy is proportional to D2 affinity
Non-D2 receptors are associated with SEs/AEs
First generation antipsychotics (FGAs)
DA antagonism = MOA
MOA characterizes “typical” anti-psychotics
Neuroleptic
Prominent D2-dopamine receptor antagonism
Typical anti psychotic
Contrasted with atypical mechanism of action of second generation anti-psychotics
Preferred term = First Generation Antipsychotic (FGA)
Examples of First Generation Antipsychotics
Fluphenazine 2-20 mg/day
Haloperidol 2-25 mg/day
Traditional Equivalent dose of FGAs
2 for both
allows for switching to equivalent dose of another FGA
Efficacy of FGA
Immediate D2 receptor blockaged
Theraputic effect develops over 6-8 weeks
Percentages of decreased presynaptic release of DA
> 60% D2 blockade = clinical response
70% D2 blockade = hyperprolactinemia
80% D2 blockage = increased risk of EPS
Adverse effects FGAs
Sedation Dystonias/Parkinsonian movement disorders (EPS) Anticholinergic effects Orthostatic hypotension Seizures Hyperprolactinemia Moderate weight gain Prolonged QT interval (incidence of sudden death 0.015% only about twice that of the healthy population)
Anticholinergic effects of antipsychotic drugs
constipation Urinary retention blurry vision tachycardia dry eyes, mouth, and throat
Antipsychotics (APs) that increase QT interval
Thioridazine
Ziprasidone
Haloperidol
QT interval inn crease in milliseconds for Thioridazine
35.8
QT interval inn crease in milliseconds for Ziprasidone
20.6
QT interval inn crease in milliseconds for Haloperidol
4.7
Early neurological adverse effects of FGAs
Acute dystonia
Akathisia
Parkinsonism
Acute dystonia w/ FGAs
1-5 days = maximal risk
Treat with:
biphenhydramine IM
benztropin IM
Akathisia w/ FGAs
5-60 days
Usual treatment for agitation is more drugs -> not in this case
Parkinsonism w/ FGAs
5-30 days
Late neurological adverse effects of FGAs
Neuroleptic malignant syndrome (weeks; 10% mortality; antiparkinson agents not effective) Tardive dyskinesia (after months - years of treatment) Perioral tremor (rabbit sundrome; months -> years)
Neuroleptic malignant syndrome (NMS)
more common in pts on high potency FGAs, depot FGAs, deyhydrated, or exhausted pts
NMS Tx
DISCONTINUE antipsychotic
DA agonist bromocriptine reduces rigidity, fever, and CK in up to 94% of pts
Amantadine (another DA agonist) works up to 63% of the time
NMS follow up
Use only SGAs for rechallenge post-NMS
Early Second Generation Antipsychotic agents (SGAs)
Clozapine Risperidone Olanzapine Quetiapine Ziprasidone Arpiprazole
Later SGA agents
Paliperidone
Iloperidone
Asenapine
Lurasidone
What additional therapeutic mechanisms do SGAs have
D1, D4 antagonism
NE, 5-HT (serotonin) antagonism
Why are SGAs atypical APs
Due to their non-D2 antagonism
Significantly less risk of extrapyramidal effects
Tradeoff of SGAs
Increased risk of metabolic effects like weight gain
Atypical APs
ability to produce antipsychotic responses with few or no acutely occurring extrapyramidal effects
Enhanced efficacy
Absence of tardive dyskinesia
Ex: clozapine (only SGA to fulfill all criteria)
SGA SE
Mod-severe weight gain DM Clozapine: 1) Seizures 2) Nocturnal salivation 3) Agranulocytosis 4) Myocarditis 5) Lens opacities
Clozapine
FDA approved despite risk of agranulocytosis (.39%)
Risk of death = 0.013%
Weekly CBCs for 6 months; then q2 weeks
Reserved for pts who fail other methods
Early SGAs
Virtually no extrapyramidal sx
Greatly reduced risk of tardive dyskinesia
Good for negative sx
Significantly less relapse than with FGAs (25% w/ Risperidone vs 40% with haloperidol)
Paliperidone (late SGA)
9-OH metabolite of risperidone
Iloperidne (late SGA)
Increased risk of orthostatic hypotension
Asenapine (late SGA)
ODT SL tabs
don’t chew or swallow
increased risk of anaphylaxis and angioedema
Schizophrenia tx
3 phases:
1) Acute
2) Stabilization
3) Maintenance
Tx of first acute psychotic episode
First goal: calm agitated pt
Immediate treatment improves long term outcomes
Most psychiatrists will prescribe SGA (not clozapine; decreased anger and anxiety seen in 24-48 hours)
Suicide risk ______ as other sx improve
Increases!!!!!!!
When do we use clozapine
Lack of response with other SGAs
Intolerable SE from other APs
Role of FGAs
Typically not first line
May be used before a SGA if chronically ill pts have a previously satisfactory response
Stage 1 pharmacotherapeutic algorithm
Only for pts w/ first schizophrenic episode
SGAs = FIRST LINE
Stage 2
pharmacotherapeutic algorithm
Chronically ill pts recently started on APs
Or new onset pt with poor response to Stage 1
Monotherapy w/ FGA or SGA
Chose different AP than used in stage 1
Stage 3 pharmacotherapeutic algorithm
Switch to clozapine (monotherapy)
Increased efficacy for suicidal behavior
Consider earlier use in suicidal pts
Monitor CBC pts (Look for agranulocytosis)
Stage 4 pharmacotherapeutic algorithm
Continue clozapine
Add additional AP (combination therapy)
Stage 5 pharmacotherapeutic algorithm
Trial of monotherapy AP
Use FGA or SGA not previously used
Stage 6 pharmacotherapeutic algorithm
Consider combination therapy
When switching APs -> overlap 2nd agent for 1-2 weeks
Taper and DC first agent (taper clozapine SLOWLY)
Combination treatment of schizophrenia
Using 2 APs simultaneously
Augmentation treatment of schizophrenia
Addition of non-AP drug to an AP
Use only in inadequately responding pts
Augmentation agents are rarely effective for schizophrenia used alone
Responders will usually improve rapidly
If no sx improvement -> DC augmentation agent
Augmentation Agents
Mood stabelizers
SSRIS
Beta blockers
Mood stabilizers as augmentation agent
Lithium
Valproic acid
Carbamazepine
Beta blockers as augmentation agents
Antiaggressive effect
Propranolol
Pindolol
Nadolol
Combination of therapy (step 4-6)
Multiple MOAs
Combos should be time limited (12 weeks)
If no improvement -> taper one and discontinue
Series of monotherapies preferred over AP combination
Maintenance tx of schizophrenia
1st presentation may respond sooner
Meds may reduce sx -> None are curative
All sx may not abate
Prevents relapse (18-32% on drugs vs. 60-80% on placebo)
Continue at least 12 months past remission
Long acting depot injectable APs
Recommended in unreliable pts
Not 1st line
Look for SE as a cause for nonadherence
Depot APs
Haloperidol decanoate (FGA) Fluphenazine decanoate (FGA) Risperidone microspheres (SGA)
Haldol lactate vs haldol decanoate
immediate vs sustained release
Haloperidol decanoate
Use 10-15xs the oral daily dose
Round dose up to nearest 50 mg
Give dose via deep IM (not IV) injection once a month
Overlap with PO haloperidol for first month
Fluphenazine decanoate
Use 1.2 times oral daily dose
Use 1.6 times PO dose for more acutely ill pts
Round up dose to nearest 12.5 mg interval
Overlap w/ PO fluphenazine for 1 week
Risperidone micropsheres
Only SGA depot agent; needs reconstitution
Optimum dose is 25-50 mg
Higher doses have no more benefit, but more EPS
Bipolar disorder
1 disorder: mania
2 disorder: hypomania
Must rule out amphetamine use and pheochromocytoma
Most distinctive syndromes in psychiatry
What did bipolar disorder used to be called
Manic depression
Bipolar disorder (BP) characterizations
Elevated mood
Overactivity
Lack of need for sleep
Increased optimism
Unique hallmark of bipolar disorder
Mania
BP mania
Different from usual behavior
Single episode significant for diagnosis
Types: one, alternating, every few year episodes
Classic bipolar disorder
Bipolar 1
manic phase-usually requires hospitalization
Major depression + hypomania
bipolar 2
Rapid cyclers and BP disorder
> 4 manic or depressive cycles per year
Genetics of BP disorder
50% of pts have family hx of BP disorder
Risk -> 10% in siblings of affected parients
Acute mania tx
Medical emergency
Marriage, job, and life of pt at risk
AP drugs = effective in acute mania
Rapid onset may be lifesaving in violent pts
Newere atypical AP (SGAs) are they effective in complaining pts
More tx for acute mania
Lithium
Valproic acid
Carbamazepine
DX for bipolar depression
Depressive episodes respond to: SSRIs, TCAs, MAOIS
Note: antidepressants may induce switch from depression to mania
Dont use AD in pts w/ hx of dangerous mania episodes
Mood stabilizers:Lithium
Classic
Good for: mania, bipolar disorder; bipolar deressin
Lithium therapeutic index
Therapuetic (acute mania) =0.6-1.2%
Tremor
Seizures/sudden death >2.5 mEq/L
Tx of bipolar depression
Depressive episodes need a response
will give SSRIs then,
Tricyclic antidepressants (TCAs)
Monoamine oxidasing inhibitors
Caution with use of antidepressants with BP disorder
Induce switch from depression to mania
Don’t use w/ h/o mania episodes
Lithium for BP disorder
Classic mood stabilizer
Good for mania, bipolar disorder, and bipolar depression (last 2 = prophylactically)
Narrow therapeutic index of Lithium
Acute mania: 0.6-1.2 mEq/L
Tremor: 1.5-2 mEq/L
Seizures/death: >2,5 mEq/L
Remember w/ lithium
Draw blood levels twice/week until stable
Collect trough samples just prior to next dose
Cabamazepine
Anticonvulsant found useful in the 80s
.5 of all doses were for bipolar illness
Weekly dosing
Valproic acid
Recent study found Li prophylaxis much more effective than valproate for suicide prevention (JAMA 2003; 290(11): 1467-73)
