Psychopharmacology – Nuts and Bolts
Medications and Things to Know:
- Always think DRUGS – in ANY DDx, could it be an adverse effect, side effect, drug-drug interaction, overdose or
noncompliance
- Pregnancy - there are basically no psychotropic drugs that are rated better than Class C
- Off label use of medications is very common in psychiatry
ANTIDEPRESSANTS
-
Overall, most of these medications have the same efficacy for treating depression, the main difference is side
effects
- Most antidepressants take a minimum of 2-4 wks to have initial efficacy; a trial of 6-8 wks at a therapeutic dose
would be considered an adequate trial for most
- Any Antidepressant may induce a manic state in pts with a predisposition (they would not require a prior
diagnosis of Bipolar disorder as this may be the sentinel event)
- There may be an inc risk for suicidal ideation in any pts taking an antidepressant
Tricyclics
Imipramine (used to treat enuresis)
Amitriptyline
Doxepin
Nortriptyline
Clomipramine
Desipramine
MoA - inhibition of serotonin and NE uptake
Indications – Depression, dysthymia, OCD, panic d/o, PTSD, chronic pain (TCA>> SSRI)
Side Effects
- Anticholinergic (dry eye, mouth, constip, urinary retention, blurred vision, AMS (inc risk in elderly 2/2 muscarinic
blockade)
- Histaminic – sedation, wt gain
- Alpha -1 adernergic blockade - orthostatic hypotension, falls
- Possilbe EKG changes, arrhythmias (prolonged QY and PR, AV block) * In OVERDOSE=widened QRS
Pearls
- Cheap but dirty
- Require diet modification to avoid HTN crisis (avoid tyramine containing foods)
- Cannot be combined with other antidepressants (risk of serotonin syndrome) or sympathomimetic drugs; avoid
with cough syrup or Demerol
- SERIOUS RISK IN OD
SSRIs
Flouxetine (Prozac)
20-80mg daily dosing range
Sertraline (Zoloft)
50-200mg/day
Paroxetine (Paxil)
20-80mg/day
Citalopram (Celexa)
20-60mg/day
Fluvoxamine (Luvox)
50-300mg/day
Escitalopram (Lexapro)
10-30mg/day
MoA – blocks reuptake of serotonin at the presynaptic nerve terminals
Indications – depression, panic d/o, OCD (typically dose upper limits), bulimia, pain d/o, GAD, social phobia, PTSD,
PMDD ; in elderely, pts with panic d/o and in children start at doses ½ the nl starting dose or less
Side Effects (SSRIs)
- GI upset, HA, insomnia, sexual dysfcn
- Hypernatremia in the elderly
- Prozac/Zoloft tend to be more activating
- Paxil tends to be more sedating
- Lovox tends to have more drug-drug interactions
Pearls
- Typically fewer side effects and very safe
- Risk of serotonin syndrome when used with other serotonin meds (SSRIS, TCAs, MAOS, demerol, St. John’s Wart)
- Serotonin Syndrome – may present as a delirium (AMS, restless, shivering, VS abnl 2/2 autonomic instability (inc
HR,BP,temp), hyperreflexia – may lead to shock, coma, death – A MEDICAL EMERGENCY
- Discontinuation syndrome – common, particularly if taper too quickly, esp with shorter acting agents (does not
happen with Prozac 2/2 long ½ life) – presents as flu-like symptoms (GI upset, sleep disturbance, mood chngs,
dizziness, lethargy – resolve when restart med
Other Antidepressants
Venlafaxine (Effexor)
dosing range 75-375mg/day
- Blocks reuptake of Serotonin and Norepinephrine
- May elevate BP
Duloxetine (Cymbalta)
dosing range 60-120mg/day
- Blocks serotonin and NE transporters; metabolized through CYP2D6 pathway – sig drug interactions
- Indications include depression and chronic pain d/o (fibromyalgia as well)
- Newer and very expensive
Buproprion (Wellbutrin, Zyban)
dosing range 75-400mg/day
- Increased dopamine activity
- Indications include MDD, dysthymia, Bipolar depression, ADHD (at low doses), used for smoking cessation
- Contraindications for use include h/o sz d/o, head trauma or anorexia/bulimia
- No sig sexual side effects
- NOT effective for anxiety; can actually worsen anxiety/agitation
Mirtazipine (Remeron)
dosing range 7.5-45mg/day
- Alpha 2 adernergic antagonist, enhances noradnergic and serotenergic
- Sedation and wt gain are sig side effects; often used in depression for those with insomnia and poor appetite; no
sig sexual side effects
- Effective in combo with SSRI for augmenting treatment of depression
Desyrel (Trazodone)
dosing range 25-600mg
- MoA includes primary inhibition of presynaptic serotonin reuptake with possible mild postsynaptic sertonertic
antagonism. Does of AEs 2/2 to histaminic, anticholinergic and alpha-1 blockades
- Used most commonly as a sleep aid rather than as antidepressant
- Effective at low doses (25mg – 200mg) for sleep, requires higher dosing for antidepressant properties (200600mg)
- PRIAPRISM in 1/6000 pts
Nefazodone (Serzone)
- Is an analog of Trazodone
- Sedating, less sexual side effects
- Many drug-drug interactions 2/2 p450 inhibition by a metabolite
- Inc risk of hepatic failure
MOOD STABILIZERS
Lithium
MoA – unclear; second messenger system effect – effect on circadian rhythms and augments serotonin fnc. Renally
cleared and can cause sig renal impairment (esp if dehydration, use of NSAIDS, thiazide diuretics and in elderly
Indications – BPAD, Schizoaffective d/o, augmentation for depression, mood lability
Side effects
- GI upset, fatigue, fine tremor, confusion
- Toxicity – AMS, N/V, slurred speech, course tremor, ataxia
- Cardiac conduction problems – 1st degree block, slowed sinus node, PVCs
- Renal impairment (DI, rare nephritic syndrome)
- Hypothyroidism in 5%
Pearls
- Pregnancy Class D – EBSTEIN’s Anomely – ht defect at tricuspid valve; avoid in 1st Trimester
- Requires blood level monitoring, has narrow therapeutic window (0.8-1.2); dialysis rec for levels greater than 4.0
- Steady state takes 5 days
- LETHAL in OD
Valproic Acid (Depakote)
MoA – unknown; ? if changes metabolism of GABA
Indications – BPAD (esp for rapid cycling mania), Schizoaffective d/o, aggression, impulse control probs
Side effects
- N/V; sedation, tremor, wt gain
- Blood abnormalities (thrombocytopenia)
- Liver dysfcn (rare hepatotoxicity) and very rare Hemorrhagic pancreatitis
Pearls
- Metabolized by liver, via P450 pathway – multitude of drug-drug interactions
- PREGNANCY CLASS D – 2/2 neural tube defects
- Requires blood level monitoring, but wide therapeutic window
- Steady state reached in 3 days
Carbamazapine (Tegretol)
- Less effective, not as widely used
- Serious side effects include blook abnl (aplastic anemia, agranulocytosis); severe rash
- Preg Class D
- Can be risky in OD, particularly 2/2 other drug-drug interactions
Lamotrigine (Lamictal)
- Used for Bipolar depression, not for manic state; commonly used for augmentation of antidepressant
medications
- 10% incidence of rash, cases of Stevens-Johnson have occurred, particularly when dosed to high too fast
- Requires slow titration to get to effective dosing (start at 25mg and inc by 25mg every 2 wks; target range is
~200mg)
Other Mood Stabilizers include other anticonvulsants (Gabapentin, Topiramate) but overall less effective and poor
outcome data
ANTI-PSYCHOTICS
-
Typical and Atypicals are equally effective (CATIE trial) for treatment of symptoms. Primary difference is side
effect profiles and new agents tend to be better tolerated
- Although some effect may seen within hours of dosing, real antipsychotic effects can take 3-6 wks to materialize
as meds reach a steady state
- Extrapyramidal Side Effects (EPS)
o Parkinsonism – shuffled gait, rigidity, masked facies, drooling, tremor
o Acute Dystonia – slow/sustained muscle contractions (neck, lock jaw, eyes); Rx with Cogentin or
Benadryl IM – scary but reversible
o Akathesia – inner restlessness, need to pace/rock; Rx with Inderal or BZDs
o Tardive Dyskinesia – often longterm, may be irreversible – abnl, invol mvmt of face, limbs, trunk. Rx but
stopping agent and changing to new antipsychotic med
- Neuroleptic Malignant Syndrome (NMS) – potentially lethal reaction to antipsychotic meds, rapid onset.
Presentation may consist of elevated temp, muscle rigidity, VS instability, AMS. Medical emergency – requires
urgent intervention and possible ICU admission, Rx w/ d/c of antipsychotic, IVF, and possibly
bromocriptine/dantrolene
Traditional Neuroleptics (Typicals, 1st Generation)
Haloperidol (Haldol)
5-20mg/day dosing range
High Potency
Trifluoperazine (Stelazine)
5-20mg/day
High Potency
Fluphenazine (Prolixin)
10-20mg/day
High Potency
Thiothixene (Navane)
5-20mg/day
High Potency
Pimozide (Orap)
1-10mg/day
High Potency
Molindone (Moban)
Loxapine (Loxitane)
Perphenizine (Trilafon)
50-100mg/day
50-100mg/day
4-40mg/day
Mid Potency
Mid Potency
Mid Potency
Mesoridazine (Serentil)
Chlopromazine (Thorazine)
Thioridizine (Mellaril)
50-400mg/day
200-800mg/day
200-800mg/day
Low Potency
Low Potency
Low Potency
MoA – Dopamine D2 receptor Antagonism (High, Mid, Low potencies depend on binding affinity)
Lower potency typically require higher dosing to elicit antipsychotic effect
Indications – Schizophrenia, psychosis 2/2 primary mood d/o/dementia/delirium, schizoaffective d/o, severe agitation,
tics
Side Effects
- Lower potency agents have more troublesome side effects 2/2 greater antagonism of cholinergic, adrenergic
and histaminergic receptors
- High potency agents have more frequent EPS effects 2/2 potent antagonism of dopa receptors
- Wt gain, sexual dysfcn, orthostatic hypotension, decreased sz threshold
- Prolonged QTc – risk of Torsades
Pearls
- Compliance is a HUGE issue and can be rare at times. Haldol and Prolixin come in injectable depot forms (req q
monthly dosing once at steady state)
Atypical Antipsychotics (new generation)
Clozapine (Clozaril)
Olanzapine (Zyprexa)
Risperidone (Risperdal)
Aripiprazole (Abilify)
Quetiapine (Seroquel)
Ziprasidone (Geodone)
400-600mg/day
5-20mg/day
1-6mg/day
10-30mg/day
200-800mg/day
80-160mg/day
Check blood levels
MoA – Prominent antagonism at Serotonin 2A receptor as well as Dopamine D2 blockade; less action on nigrostriatal
pathway (where EPS Symptoms are thought to originate)
Indications – same as above
Side Effects
- Clozapine – Agranulocytosis in 1-2%, requires CBCs weekly while starting, monthly forever; lowers sz threshold.
Myocarditis. Commonly causes tachycardia, hypotension, drooling
- Common SEs for all include metabolic syndrome (wt gain, hypercholesterol, DM); sedation, orthostatic
hypotension
- EPS lower frequency; inc frequency in pts who are neuroleptic niave
- TD much less incidence, but may still occur
- Cardiac side effects, QTc prolongation; independent cardiovasc risk for all taking atyipcals (inc risk of ischemic
stroke) – despite length of time taking
- Risperdal has risk of elevated prolactin (amenorrhea, gynecomastia, galactorrhea and impotence)
Pearls
- Risperdal comes in long acting injectable
- Abilify, Geodone, Zyprexa come in short acting injectable (often used in acute settings)
- Abilify, Risperdal, Zyprexa all come in dissolvable tablet formulation (helpful for noncompliance)
- Have benefit in treating particularly negative symptoms and most have mood stabilization properities (Seroquel,
Abilify and Geodone have FDA approval as primary agents for BPAD manic/mixed state)
- Clozaril is the go to agent for treatment refractory schizophrenia
ANTIPARKINSONIAN DRUGS
Benztropine (Cogentin)
Trihexyphenidyl (Artane)
Biperiden (Akineton)
MoA – Anticholinergic effect, restores ACh/Dopa balance
Indications – treatment of EPS side effects assoc w/ antipsychotic drugs
Side Effects
- Dry mouth, blurred vision, constipation, confusion/AMS, delirium
Pearls
- Artane has euphorigenic properties and is at risk of being abused
- Amantadine is an alternative treatment (mech is a dopa agonist)
ANTI-ANXIETY MEDICATIONS
SSRIs – see above
Benzodiazepines *these are controlled substances
Clonazepam (Klonopin)
18-50hr ½ life
Alprazolam (Xanax)
6-12hr ½ life
Lorazepam (Ativan)
10-20hr ½ life
Diazepam (Valium)
20-100hr ½ life
Chlordiazepoxide (Librium)
5/30hr ½ life
Clorazepate (Tranxene)
36-200hr ½ life
MoA (BZDS) – work at GABA receptor (like EtOH) to cause CNS depression
Indications – panic d/o, severe anxiety, agitation, agitated depression, social phobia, akathesia, insomnia, acute EtOH
withdrawal. Often used for initial treatment of anxiety until SSRI therapeutic
Side Effects
- Sedation, drowsiness, dizziness (Feelings of being intoxicated)
- Delirium, Respiratory suppression
- Dependence formation (physiological as well as psychological); AKA can develop tolerance
Pearls
- Just as EtOH, physical dependence can lead to withdrawal syndrome upon abrupt cessation as well as risk of
seizure, coma and death
- Caution in gero population, metabolites can often build up excessively with significantly prolonged ½ lives and
dangerous blood levels – recommend minimal use to avoidance
- Can be lethal in OD
Buspirone (BuSpar) not a controlled substance
- Mild effect for GAD; may be used for augmentation of antidepressant treatment
- Common SEs HA, N/V, dizziness
- No risk of dependence or developing tolerance
- Safe in OD
Hydroxyzine (Vistaril, Atarax) not a controlled substance
- MoA – antihistaminic (used for treatment of anxiety as well as purities)
- Likely deliriogenic in elderly 2/2 anticholinergic properties
SUBSTANCE ABUSE
Disulfuram (Antabuse)
- Req pt to be strongly motivated, only by taking than causes severe rxn if EtOH ingested (N/V)
- Contraindicated if pt with liver dis
Naltrexone (Revia)
- Dec craving by targeting “pleasure pathway” in brain
- Often pts will dec but not completely abstain from use
Methadone – controlled substance
- Rx of heroin dependence
Buprenorphine (Suboxone) – controlled substance
- Tx opioid dependence
DEMENTIA
Acetylcholinesterase Inhibitors (used to treat mild-moderate dementia of Alzheimer’s type)
Donepezil (Aricept) – reversible, selective inhib
o Decreases breakdown of Acetylcholine in brain ( inhibits acetylcholinesterase)
o More specific and less GI side effects
Rivastigmine (Exelon) – reversible, selective inhib
o also available as a patch
Galantamine (Reminyl) – reversible, competitive inhib
NMDA Antagonist (used to treat moderate to severe dementia of Alzheimer’s type)
Memantine (Namenda)- noncompetitive NMDA antagonist, reduces glutamate
mediated excitotoxicity
Vitamin E – antioxidant, thought to prevent cell death
HYPNOTICS
Benzodiazepines
Zolpidem (Ambien)
Zaleplon (Sonata)
Eszopiclone (Lunseta)
Desyrel (Trazodone)
ADHD MEDICATIONS
Stimulants
- All work equally well, but individuals may differ in response
- Quick onset of action and effect (same day is possible)
- May require multiple daily doses
- All stimulants are controlled substances
- FDA Approval – Adderall and Dexedrine for age 3 and up; all other stimulants for age 6 and up
Methylphenidate
o Short Acting forms (Ritalin, Methylin, Focalin)
o Long-Acting forms (Ritalin LA and SR, Metadate ER and CD, Methylin ER, Focalin XR, Concerta, Daytrana
Patch)
Amphetamines
o Short-Acting forms (Adderall, Dexedrine, Dextrostat, Desoxyn)
o Long-Acting forms (Adderall XR, Dexedrine Spansule, Vyvanse)
Atomoxetine (Strattera)
- MoA more like antidepressant than stimulant
- Gen considered 2nd line; recommendation would be to try 3 separate stimulant trials prior to starting
- Consider 1st line when h/o substance abuse, h/o anxiety or parents requesting non-controlled substance
- FDA approved from age 6 and above
- May take weeks to be effective, requires daily use and strict compliance
- Same black box warnings as antidepressants
Non-FDA Approved – 2nd to 3rd line agents
Buproprion
Modafanil (used for treatment of narcolepsy)
Clonidine (antihypertensive; also used in children for treatment of aggression/agitation)
Amantadine (treatment for influenza, MoA – dopamine agonist)