Psycho Tri Pic Medications

8/6/2019 Psycho Tri Pic Medications

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Psychotropic

MedicationsDale Sanderson, PA-C

Physician Assistant

Seattle Mental Health


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Overview SSRI antidepressants

Atypical antidepressants Tricyclic antidepressants MAOI antidepressants Older mood stabilizers

Newer mood stabilizers Older antipsychotics Newer antipsychoticsAnticholinergics Benzodiazepines

Other anxiolytic/hypnotics Stimulants Meds for dementia Meds for substance abuse Psychiatric uses of antihypertensives


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Introduction

SSRI antidepressantsAtypical antidepressantsTricyclic antidepressantsMAOI antidepressantsOlder mood stabilizersNewer mood stabilizersOlder antipsychoticsNewer antipsychotics

AnticholinergicsBenzodiazepinesOther anxiolytic/hypnoticsStimulantsMeds for dementiaMeds for substance abusePsychiatric uses of

antihypertensives

FDA approval process

Advantages & limitations

driven by publics concerns aboutsafety study population vs. real world drug company agenda for approval

Indication vs. off-label use and dosing

1982 position report Side-effect listing

cause & effect?


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Introduction Choosing a medication

diagnosis

benefit vs. side-effects, toxicity, ease of use, drug-druginteractions (www.drug-interactions.com, www.drugs.com )

medication history, family history

Starting, stopping & changing luxury of time

cross tapering

one change at a time

Response rate response vs. remission

the right diagnosis

treatment failures


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SSRI antidepressants

SSRIantidepressants

Atypical antidepressantsTricyclic antidepressantsMAOI antidepressants

Older mood stabilizersNewer mood stabilizersOlder antipsychoticsNewer antipsychotics

AnticholinergicsBenzodiazepinesOther anxiolytic/hypnotics

StimulantsMeds for dementiaMeds for substance abusePsychiatric uses of

antihypertensives

Selective SerotoninReuptake Inhibitor

1988 Prozac introduced 1992-93 Zoloft, Paxil, Luvox

1998 Celexa 2001 fluoxetine (Prozac generic) 2002 Lexapro (modified Celexa) 2006 STAR*D trial results published

http://www.nmha.org/research/star/faqs.cfm

Annual sales = $12 billionNumber of patient starts on Prozac, Paxil or Zoloft

from 1988 to 2002 = 67.5 million(www.ahrp.org)


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Mechanism of action Inhibit serotonin reuptake so increase synaptic

serotonin levels

Many SSRIs affect other receptors especially at high

doses Clinical effect usually takes weeks so mechanism

goes beyond simply increasing synaptic serotoninlevels

Several serotonin (5-HT) receptor subtypes

Serotonin receptors are located throughout the body(especially GI tract)


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Indications & off-label uses All except Luvox FDA approved to tx depression (major

depressive d/o and dysthymia)

Various class members also approved to treat:generalized anxiety d/o, OCD, panic d/o, PTSD, eatingdisorders, premenstrual dysphoric d/o, social anxietyd/o

Off-label uses- ADHD, insomnia, chronic painsyndromes, seasonal affective d/o, behavioralproblems in individuals with dementia and mentalretardation, other uses


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Half-life Short: paroxetine & fluvoxamine (missed doses

can result in uncomfortable symptoms)

Moderate: sertraline, citalopram, escitalopram

Long: fluoxetine (good for people who may missdoses)


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Side effects Decreased sex drive and impaired sexual function

tend not to resolve with time

Nausea, diarrhea, anorexia, vomiting

- all increase with dose and can resolve with time

Weight gain (esp. paroxetine) after initial GI effects

Headache, dizziness, anxiety (esp. fluoxetine), rash,

insomnia, sedation, sweating, vivid dreams, tremor,dry mouth (esp. paroxetine), bruising, prolactin


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Drug-drug interactions (DDI) Luvox > Prozac > Paxil > Zoloft > Celexa > Lexapro

Interacting effects may be dose dependent (Zoloft)

SSRI levels tend not to be altered by other drugs butcan potentially increase levels (inhibit metabolism) ofcertain drugs

Examples:

paroxetine > risperidone

fluoxetine > buspirone

fluvoxamine > olanzapine(consult references such as www.drug-interactions.com, www.drugs.com, others)


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Cautions Suicidal ideation and suicide risk especially with children

early in tx but significant debate

Serotonin syndrome (SSRI + MAOI, possibly lithium, others)

>> diarrhea, tremor, sweating, restlessness,hyperreflexia

progression ofsymptomsifuntreated

>> disorientation, rigidity, fever >> coma, seizures >>

>> death (approximately 10% mortality rate)

Many medications/substances have serotonin activity:

dextromethorphan, fentanyl, meperidine, sumatriptan,

St Johns Wort, MDMA (ecstasy), LSD, many others


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citalopram (Celexa) Few drug-drug interactions (DDIs)

High serotonin specificity

Typical or less SSRI side effects

escitalopram (

Lexapro)

no generic available

Simple dosing

S molecule of the S & R mirror-image mixture ofcitalopram molecules

fluoxetine (Prozac, Sarafem, Symbyax- with Zyprexa)

Very long half-life

Significant DDIs

Can be activating


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SSRI antidepressants fluvoxamine (Luvox)

OCD indication

Multiple significant DDIs

paroxetine (Paxil)

Significant DDIs

Some reports of associated weight gain

Withdrawal symptoms with missed doses

sertraline (Zoloft)

Moderate DDIs

Multi-step dosing


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Atypical antidepressants


Atypical

antidepressantsTricyclic antidepressantsMAOI antidepressantsOlder mood stabilizersNewer mood stabilizersOlder antipsychoticsNewer antipsychoticsAnticholinergicsBenzodiazepinesOther anxiolytic/hypnoticsStimulantsMeds for dementiaMeds for substance abusePsychiatric uses of

antihypertensives

Newer antidepressants that arenot/less serotonin specific oraffect serotonin differently thanSSRIs

1981- Desyrel (trazodone)1989- Wellbutrin (bupropion)1993- Effexor (venlafaxine)1994- Serzone (nefazodone)

1996- Remeron (mirtazapine)2004- Serzone discontinued although

generics still available2004- Duloxetine (Cymbalta)


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Mechanism of action venlafaxine and duloxetine are both serotonin and

norepinepherine reuptake inhibitors- SNRIs

mirtazapine has serotonin subtype & norepinephrine

activity trazodone, nefazodone have different serotonin activity

than SSRIs

bupropion has dopamine and norepinephrine activity


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Indications & off-label uses All have FDA approval to treat depression

SNRIs shown effective in chronic neuropathic pain

Nicotine addiction (bupropion)

Augment SSRIs, reduce (?) SSRI sexual side effects

Insomnia (mirtazepine, trazodone)

Many similar uses to SSRIs

bupropion, mirtazepine, trazodone & nefazodone donot usually have associated sexual dysfunction


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venlafaxine (Effexor) Similar to TCAs with less safety & side effect concerns

FDA approval for depression and generalized anxietyd/o & social anxiety d/o

SNRI- activity depends on dose Minimal DDI

SE with missed doses

duloxetine (Cymbalta) SNRI profile minimally dose dependent

Indicated for depression & chronic neuropathic pain


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bupropion (Wellbutrin, Zyban) NE, dopamine reuptake inhibition

Can be activating

Zyban to tx smoking addiction

Seizure risk in certain patients ( risk at dose)

Potential DDIs not often significant (except MAOIs)

mirtazapine (Remeron) Complex serotonin, NE (2) & histamine activity

Receptor activity changes with changes in dose

Sedation & weight gain especially at lower dose

Lipid abnormalities

Minimal DDIs (except MAOIs)


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nefazodone (Serzone) Rarely used due to irreversible liver toxicity

Pulled from market by initial manufacturer in 2004although still available as generic

Still popular with some patients

trazodone (Desyrel) Sedation, weight gain, low blood pressure

Used most commonly (off label) for insomnia Rare reports of sustained painful erection (priapism)

that should be treated in ER (can lead to impotence)


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Tricyclic antidepressants

SSRI antidepressantsAtypical antidepressants

Tricyclicantidepressants

MAOI antidepressantsOlder mood stabilizersNewer mood stabilizersOlder antipsychoticsNewer antipsychotics


StimulantsMeds for dementiaMeds for substance

abusePsychiatric uses of non-

psychotropic meds

Describes a group of drugs withsimilar structure and function(abbreviated as TCA)

1958- imipramine failed investigationas an antipsychotic but found tohave antidepressant properties.

1960s- multiple otherTCAs developedand placed into use

1990s- significant reduction in use due tointroduction of SSRIs which havefewer side effects


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Mechanism of action Norepinephrine, serotonin, histamine, muscarinic (cholinergic)

and -adrenergic receptor activity although in differing ratios

Anticholinergic activity leads to many of the side effects ofthese drugs

Indications & off-label uses Depression and similar spectrum of disorders as SSRIs

Especially helpful with chronic pain and depression secondaryto medical conditions such as AIDS

enuresis, narcolepsy, premature ejaculation, insomnia,migraine prophylaxis

Blood levels: May be obtained to monitor dose effectiveness


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Drug-drug interactions (DDI) Multiple significant interactions in each direction with

potentially serious consequences

Side effects (SE) Anticholinergic SE include: dry mouth, constipation, blurred

vision and urinary retention Cardiac arrhythmias and conduction changes

Orthostatic hypotension

Sedation

Weight gain

Cautions Overdose is frequently fatal

Pts with bipolar d/o may be pushed into mania or rapid cycling


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Tricyclic antidepressantsN

E 5HT

Ach Sed Commentsamitriptyline (Elavil)low high high high pain, MgrHA

amoxapine (Asendin) high low mod low tetracyclic

clomipramine (Anafranil). low high high high tx OCD; SSRI-like

desipramine (Norpramin) high low low low activating

doxepin (Sinequan). low low mod high used for insomniaimipramine (Tofranil). low low mod mod pain; enuresis

maprotiline (Ludiomil) high low low mod tetracyclic

nortriptyline (Pamelor).. mod low mod mod chronic pain

protriptyline (Vivactil) high low mod low most activating

trimipramine (Surmontil).. low low high high

NE- noropinephrine activity; 5HT- serotonin activity (5-hydroxy-tryptamine); OCD:Obsessive-compulsive d/o

Ach- anticholinergic effects; Sed- sedation; mod-moderate; MgrHA- migraine headache prophylaxis


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Monoamine Oxidase Inhibitors

SSRI antidepressantsAtypical antidepressants


MAOIantidepressants

Older mood stabilizers

Newer mood stabilizersOlder antipsychoticsNewer antipsychotics

AnticholinergicsBenzodiazepinesOther anxiolytic/hypnoticsStimulants

Meds for dementiaMeds for substance abusePsychiatric uses of

antihypertensives

Abbreviated as MAOI

1952- First MAOI found with antidepressantproperties in process of looking for anantituberculosis drug

1962- Investigation of a death from hypertensivecrisis by someone ingesting tyramine rich

food while taking an MAOI1960s- Institution of strict dietary restriction of

tyramine containing foods and otherinteracting substances.

1960s- Significant reduction in use due tointroduction ofTCAs which do not have

the severe restrictions of MAOIs.2006- Transdermal selegiline patch (Emsam)approved to treat depression


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Features Effective antidepressant for those who can adhere to the

necessary restrictions and tolerate many other side effects

Very long duration requiring caution when mixing withrestricted substances or medications

Tyramine containing foods (not a complete list) Certain ones may be consumed in moderation

Many cheeses, chocolate, soybeans, hot dogs, drysausage, caffeine, beer, wine, pickles, olives, etc.

Drug-drug interactions Multiple prescribed and over-the-counter medications can

be potentially lethal. Serotonin syndrome with SSRIs &many others.


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Available formulations phenylzine (Nardil);

isocarboxazid (Marplan);

tranylcypromine (Parnate)

Similar medications

selegiline (Eldepryl) used to treat Parkinsons symptoms

selective B inhibitor at low doses so restrictions not critical

at higher doses acts like typical MAOI and so need restrictions

recently available as transdermal patch (Emsam) to tx depression

and not needing food restrictions at low dose although still DDI reversible selective A inhibitors not available in US (no

restrictions)


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Mood Stabilizers- Introduction

Treat bipolar disorder (manic-depressive disorder) Many used to treat various seizure d/o types,

migraines, chronic pain syndromes, aggression,impulsivity, augmentation of antidepressants and

antipsychotics Other classes of meds also used in bipolar

treatment usually in combination with moodstabilizers

Treatment of acute mania vs. prophylaxis vs.depression


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Older Mood Stabilizers

SSRI antidepressantsAtypical antidepressantsTricyclic antidepressantsMAOI antidepressants

Older moodstabilizers

Newer mood stabilizersOlder antipsychoticsNewer antipsychotics


StimulantsMeds for dementiaMeds for substance abusePsychiatric uses of

antihypertensives

Lithium, carbamazepine & valproicacid

1949- lithium recognized as antimanic1949- lithium toxicity identified after being

used as substitute for sodium in salt

1966- French researchers demonstratevalproates efficacy in treating mania

1978- significant studies demonstratelithiums efficacy in bipolar disorder

1980 studies demonstrate effectiveness ofcarbamazepine in bipolar d/o


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Lithium- features Only mood stabilizer without significant anticonvulsant

properties

up to 70% response rate

demonstrated effectiveness in reducing suicidality

less effective in rapid cycling and mixed bipolar states

full clinical effect may take up to 1-2 months

serum levels guide dosing

lab draw 8-12 hrs after last dose

excreted through the kidneys minimal liver mediated drug-drug interactions (but see

next slide for other medication issues)


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Lithium- side effects fine tremor, weight gain, nausea

increased thirst and urination

more severe toxicities include coarse tremor, gaitinstability, vomiting, diarrhea, confusion

increased risk of toxicity with fluid or salt restriction, hotweather/sweating, use of anti-inflammatory drugs, aceinhibitors & angiotensin receptor blockers, diuretics

may cause kidney and thyroid dysfunction so regular

monitoring of creatinine,B

UN

andT

SH are necessary females are at much greater risk of lithium related thyroid

dysfunction


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Carbamazepine (Tegretol)- features used in acute mania and bipolar maintenance

more effective than lithium in rapid cycling & mixed states

less effective in bipolar related depression

serum levels can be helpful in guiding dosing lab draws 8-12 hours after last dose

multiple significant drug-drug interactions (DDI) affectingboth other medications (reducing their levels) & other

medications affecting it (increasing carbamazepine levels) induces its own metabolism so may need to adjust dose

over several weeks


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Valproic acid (valproate, Depakote)- features can be dosed rapidly to treat acute mania

more effective than lithium in rapid cycling & mixed states

used by some to treat aggression and impulsivity in otherpsychiatric disorders

approved for migraine prophylaxis

serum levels can be helpful in guiding dosing

lab draws 8-12 hours after last dose

commonly used at top or above levels stated for seizure

control some suggest supplementation with carnitine, selenium

and others to reduce side effects


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Valproic acid (Depakote)- side effects nausea, weight gain, unsteadiness (ataxia), hair loss,

tremor

liver dysfunction, decreased platelets (thrombocytopenia)

pancreatitis (rare but potentially serious) polycystic ovary disease suggested by some reports

ammonia levels can be increased particularly in thoserare individuals with genetic metabolic deficits

drug-drug interactions by various mechanisms withnumerous other anticonvulsants, aspirin and others


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Newer Mood Stabilizers

SSRI antidepressantsAtypical antidepressantsTricyclic antidepressantsMAOI antidepressantsOlder mood stabilizers

Newer moodstabilizers

Older antipsychoticsNewer antipsychotics

AnticholinergicsBenzodiazepinesOther anxiolytic/hypnoticsStimulantsMeds for dementiaMeds for substance abusePsychiatric uses of

antihypertensives

lamotrigine, oxcarbazepine, topiramate,

(levatiracetam, zonisamide)

1990s- lamotrigine investigated formood stabilizing properties afterpts on it for seizure disorders

report benefits1990s- most newer approved

anticonvulsants are investigatedfor mood stabilizing properties

2003- lamotrigine approved for bipolar I

maintenance


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Lamotrigine (Lamictal) Minimally sedating unlike most other mood stabilizers

Appears to be especially effective in treated bipolardepression but unproven to treat mania

Early use as an anticonvulsant in children raisedconcerns about potentially life-threatening rash (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Initiating lamotrigine is done very slowly to decrease rashrisk

valproate greatly increases lamotrigine levels

carbamazepine greatly decreases lamotrigine levels


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Oxcarbazepine (Trileptal) Used primarily in combination with other mood stabilizers

although efficacy not clearly substantiated

Modified carbamazepine with potentially less side effects anddrug-drug interactions than carbamazepine

10,11-carbamazepine epoxide not a metabolite so higher doserequired if switching from carbamazepine

Topiramate (Topamax) Research questions its use as a mood stabilizer although

scattered reports suggest possible benefit

weight loss, cognitive dulling, kidney stones, metabolic acidosis


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Levatiracetam (Keppra) Efficacy in bipolar disorder unsubstantiated although scattered

reports suggest possible benefit

Minimal drug-drug interactions

Zonisamide (Zonegran) Efficacy in bipolar disorder unsubstantiated although scattered

reports suggest possible benefit

Side effects similar to topiramate including weight loss

Olanzapine/fluoxetine combination (Symbyax) approved to treat bipolar depression


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OlderAntipsychotics Neuroleptic

seize the neuron referring to the tendency to cause stiffness andother neurologic symptoms

early methods of dosing would achieve neurolepsis and then backdose down to relieve this effect

Major tranquilizer refers to the tendency to sedate, quiet and create a blandness in

patients similar to the negative symptoms of schizophrenia

differentiates from the benzodiazepines (Valium etc.) which werereferred to as minor tranquilizers

Typical, traditional, conventional antipsychotics

differentiates these drugs from newer atypical antipsychotics Dopamine receptor antagonist

highlights strong dopamine activity and tight binding at D2 receptors


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OlderAntipsychotics

Side effect terminology: Extrapyramidal symptoms (EPS)

pyramidal system- responsible for voluntary movement

extrapyramidal system- responsible for involuntary muscle action

includes dystonias, Parkinsonism, akathisia & tardive dyskinesia

Acute dystonia sustained muscular contraction of neck, eyes, throat

generally occurs soon after starting medication

Akathisia uncomfortable continuous motor restlessness can occur any time in treatment but generally in first week(s)

easily misdiagnosed as the underlying psychiatric disorder


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OlderAntipsychotics

Side effect terminology contd: Parkinsonism

tremor, muscle stiffness, slowed movement, drooling

generally occurs beyond 1 week after starting medication

Tardive dyskinesia (TD) spastic facial distortions and tongue movements

may extend to neck, trunk, and extremities

delayed effect, usually beyond 6 months from starting medication

risk increases with duration of exposure to antipsychotic

known to occur without antipsychotic therapy may be permanent, occur on discontinuation or resolve on own

is worsened by medications used to treat other EPS symptoms


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OlderAntipsychotics

Side effect terminology contd: Neuroleptic malignant syndrome (NMS)

pipe-like rigidity, fever, tremor, altered level of consciousness

hypotension, tachycardia

laboratory abnormalities- elevated WBC & CK

mortality 10-20%

can occur any time in course of treatment

Anticholinergic effects dry mouth, blurred vision, constipation, urinary retention, mydriasis

(dilated pupils)


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OlderAntipsychotics

Methods of classification: Structure aliphatic phenothiazine - chlorpromazine

piperazine phenothiazine -perphenazine,trifluoperazine,fluphenazine

piperidine phenothiazine - thioridazine,mesoridazine thioxanthene- thiothixene

dibenzodiazepine- loxapine

indolone- molindone

butyrophenone- haloperidol

diphenylbutylpiperidine- pimozide


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OlderAntipsychotics

Methods of classification: Clinical effect/potency

Low potency: chlorpromazine,mesoridazine, thioridazine medium-high sedation, low-medium EPS, high AC

Medium potency:perphenazine,loxapine,molindone

low-medium sedation, high EPS, low-medium AC High potency: fluphenazine, trifluoperizine, thiothixene,

haloperidol, pimozide

medium-low sedation, high EPS, low AC

EPS:extrapyramidalsymptoms

AC:anticholinergiceffects


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OlderAntipsychoticsLow chlorpromazine (Thorazine) cardiac risk, weight gain

High fluphenazine (Prolixin) long-acting injection available

High haloperidol (Haldol) long-acting injection available

Med loxapine (Loxitane)

Low mesoridazine (Serentil) cardiac riskMed molindone (Moban)

Med perphenazine (Trilafon) good outcome in CATIE trial

High pimozide (Orap) cardiac risk

Low thioridazine (Mellaril) high cardiac riskHigh thiothixene (Navane)

High trifluoperazine (Stelazine)


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NewerAntipsychotics

SSRI antidepressantsAtypical antidepressantsTricyclic antidepressantsMAOI antidepressantsOlder mood stabilizersNewer mood stabilizersOlder antipsychotics

Newerantipsychotics

AnticholinergicsBenzodiazepinesOther anxiolytic/hypnoticsStimulants

Meds for dementiaMeds for substance

abusePsychiatric uses of

antihypertensives

1990 clozapine introduced in US afterlong delay related to safetyconcerns

1994 risperidone1996 olanzapine

1997 quetiapine2000 ziprasidone2003 aripiprazole2004 ADA/APA consensus report on

obesity & diabetes in those takingantipsychotics

http://care.diabetesjournals.org/cgi/content/full/27/2/596


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NewerAntipsychotics

Terminology Atypical antipsychotics, Second-generation antipsychotics,

Serotonin-dopamine antagonists

Mechanism adds serotonin (5HT 2A) activity

binds more loosely to dopamine receptors clozapine initially rejected as an antipsychotic because of its

seemingly reduced dopamine impact and lack of EPS

Indications/uses

schizophrenia and other psychotic disorders acute bipolar mania & maintenance

augmentation of antidepressants & mood stabilizers

aggression & impulsivity


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NewerAntipsychotics aripiprazole (Abilify)

unique complex mechanism can be either activating or sedating, nausea common

clozapine (Clozaril) most effective antipsychotic

risk of agranulocytosis (decreased neutrophil WBCs) CBC weekly x 6 mos, bi-weekly x 6 mos, then monthly

multiple other side effects & DDI

levels reduced by smoking

olanzapine (Zyprexa, Zydis) significant weight, diabetes and lipid abnormality risk

levels reduced by smoking


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NewerAntipsychotics

quetiapine (Seroquel) approved dose range considered low by many

low EPS risk

used commonly as sedating agent

risperidone (Risperdal) most like typical antipsychotics at higher doses

available in long acting injection (Consta)

ziprasidone (Geodon) approved dose range considered low by many

initial cardiac concerns appear insignificant for most

must be taken with fat-containing meal/snack


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Anticholinergics (AC)

SSRI antidepressantsAtypical antidepressantsTricyclic antidepressantsMAOI antidepressantsOlder mood stabilizersNewer mood stabilizers

Older antipsychoticsNewer antipsychotics

AnticholinergicsBenzodiazepinesOther anxiolytic/hypnoticsStimulantsMeds for dementia

Meds for substanceabuse

Psychiatric uses ofantihypertensives

benztropine (Cogentin) least sedating, most commonly used

biperiden (Akineton)diphenhydramine (Benadryl)trihexyphenidyl (Artane)

amantadine (Symmetrel) not an AC, used rarely to treat EPS

Treats extrapyramidal symptoms (EPS) tremor, stiffness, drooloing, dystonias akathisia may not respond to ACs tardive dyskinesia may worsen with ACs

Dry mouth, constipation, blurred vision EPS thought to be cholinergic/

dopamine imbalance


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Benzodiazepines


Newer antipsychoticsAnticholinergics

BenzodiazepinesOther anxiolytic/hypnoticsStimulantsMeds for dementiaMeds for substance


antihypertensives

1957 Librium (chlordiazepoxide)

1970s Valium (diazepam) top sellingdrug in US

1986 Xanax (alprazolam) top sellingdrug in US

1990s SSRIs replace some chronicbenzodiazepine use for anxiety


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Benzodiazepines (BZ) General characteristics

Differ in action, duration, drug-drug interactions & sideeffects based on differences in absorption rate, lipidsolubility & metabolism.

Indications/uses include anxiety d/o, panic d/o, mania,seizure d/o, phobias, insomnia, alcohol withdrawal,muscle spasm, agitation, catatonia, akathisia

hospital use (IV/IM) in sedation for procedures

Side effects sedation, cognitive impairment, anterograde amnesia

respiratory depression at high dose or with alcohol may worsen obstructive sleep apnea symptoms

disinhibition in susceptible individuals


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Benzodiazepinesalprazolam (Xanax) short-mid

chlordiazepoxide (Librium) long

clonazepam (Klonopin) mid-long serotonergic?

clorazepate (Tranxene) long

diazepam (Valium) long

estazolam (ProSom) mid

flurazepam (Dalmane) long

lorazepam (Ativan) short-mid min DDI

oxazepam (Serax) short-mid min DDI

temazepam (Restoril) mid min DDItriazolam (Halcion) short common procedure presedate


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Other anxiolytic/ hypnotics


AnticholinergicsBenzodiazepines

Other anxiolytic/hypnotics

Stimulants

Meds for dementiaMeds for substanceabuse


1869- chloral hydrate first used

1992- Ambien approved2006- zolpidem (Ambien) generic

Hypnotics = medications to inducesleep

Non-benzodiazepine anxiolytics includebuspirone & antihistamines.

Newer anticonvulsants are used off-labelas both anxiolytics and hypnoticsalthough efficacy is unproven.

Trazodone and some tricyclicantidepressants are used as hypnotics

Newer hypnotics active at GABA 1receptor except ramelteon


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Miscellaneous

buspirone (BuSpar)- subtle anxiolytic, slow response

chloral hydrate (Noctec)- hypnotic, rapid tolerance, toxicity inoverdose

Antihistamines

hydroxyzine pamoate (Vistaril)

diphenhydramine (Benadryl)

Anticonvulsants- mildly sedating and calming

gabapentin (Neurontin)

pregabalin (Lyrica)

tiagabine (Gabatril)


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Selective benzodiazepine receptor activity (GABA 1)-hypnotics

eszopiclone (Lunesta) - long-term use approval

zaleplon (Sonata) - short half-life

zolpidem (Ambien)

Melatonin receptor agonist

ramelteon (Rozeram)


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Stimulants / ADHDDrugs

atomoxetine (Strattera)- non-stimulant treatment for ADHD

recent caution about suicidal ideation

rare liver function impairment

clonidine (Catapres) antihypertensive alpha 2 agonist

used for ADHD, substance withdrawal, Tourettes syndrome,others

pemoline (Cylert) rarely used stimulant due to liver toxicity


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Stimulants / ADHDDrugs

dextroamphetamine (Dexedrine) multiple long-acting forms

insomnia, headache, tremor, exacerbation of tics, nausea,weight loss, blurred vision, overstimulation

methylphenidate (Ritalin) see notes above for dextramphetamine

modafinil (Provigil) non-stimulant

poorly understood mechanism of action

used for sleepiness related to narcolepsy, obstructivesleep apnea, depression, multiple sclerosis

use for ADHD being investigated


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Medications forDementia


AnticholinergicsBenzodiazepinesOther

anxiolytic/hypnoticsStimulants

Meds for dementiaMeds for substance


antihypertensives

1993 Cognex (tacrine) approved

1996 Aricept (donepezil) approved

1997 Generalizability of approval studiesquestioned (J Am Ger Soc 1997;45:923)

2003 Namenda approved for moderate tosevere Alzheimers Dementia

2004 Detailed British study questionsefficacy of cholinesterase inhibitors


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General characteristics

The search for a treatment for Alzheimers Dementia isdriven by intense human suffering & immensedemographic numbers.

Studies that support use of these medications generally

find subtle benefit or slowing of decline.

There is significant debate about the benefit vs. cost ($$& side effects) of using these medications.

Treatment for behavioral issues in dementia has been

complicated by FDA warnings about the risk of usingantipsychotics in the elderly.


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Cholinesterase inhibitors address one theorized mechanism of this complex disease

donepezil (Aricept)

galantamine (Reminyl)

rivastigmine (Exelon) tacrine (Cognex)

rarely used due to liver toxicity

___________________________________

memantine (Namenda) complex activity via NMDA (glutamate mediated) receptor

may have more broad psychiatric application


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Meds to TxSubstance Abuse


Newer antipsychoticsAnticholinergicsBenzodiazepinesOther

anxiolytic/hypnoticsStimulantsMeds for dementia

Meds to treatsubstance abuse


Use of medications in substance

abuse: Treat withdrawal symptoms

benzodiazepines (BZ),anticonvulsants, clonidine

Treat comorbid psychiatricdisorders anxiety & depression are common both primary & secondary etiologies SSRIs, mood stabilizers, BZ (??)

Prevent relapse deterrents, craving control


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disulfiram (Antabuse)

deterrent

requires motivated patient

acamprosate (Campral)

craving control TID dosing, minimal DDI

efficacy shown in some studies with more severealcoholics although other studies question efficacy


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naltrexone (ReVia)

opioid antagonist

COMBINE study demonstrates effectiveness in reducingrelapse with medical management sessions (JAMA2006;295:2003-2017)

high response for placebo cause some to question studydesign

http://www.niaaa.nih.gov/NewsEvents/NewsReleases/COMBINERelease.htm

potential liver toxicity

Vivitrol injectable naltrexone lasts 30 days www.vivitrol.comnot part of the COMBINE study


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buprenorphine/naloxone (Suboxone)

treatment for opioid dependence

contains both an agonist & antagonist

bupropion (Zyban)

identical to Wellbutrin treats nicotine craving

Others:

several anticonvulsants (topiramate, etc.) have beenused for craving reduction

Disabilities & alcoholism resource:http://pubs.niaaa.nih.gov/publications/social/module10idisibilities/module10i.html


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Psychiatric uses of antihypertensives


Newer antipsychoticsAnticholinergicsBenzodiazepinesOther anxiolytic/hypnoticsStimulantsMeds for dementiaMeds for substance

abusePsychiatric

uses of

antihypertensives

The uses of these drugs are off-label and carry additionalpotential side effects from theircardiovascular actions.

Potential psychiatric benefits haveoften been discovered while theseagents were used for their primaryindication.

Monitor blood pressure


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Psychiatric uses of antihypertensives

alpha (2) adrenergic agonists clonidine, guanfacine, prazosin used in ADHD, Tourettes syndrome, PTSD prazosin found helpful in reducing PTSD related nightmares

beta blockers propranolol (Inderal) used for akathisia, lithium-induced tremor,

performance anxiety & aggressive behavior (hyperarousal) pindolol has been considered for antidepressant augmentation multiple DDIs avoid in asthma, diabetics on insulin, certain cardiovascular diseases

calcium channel blockers diltiazem, verapamil, nimodipine may be helpful as additional agent in bipolar maintenance multiple DDIs and precautions


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ReferencesAlbers, L. J., Hahn, R. K., & Reist, C. (2005). Handbook ofpsychiatricdrugs.

Laguna Hills, CA: Current Clinical Strategies Publishing.

Carlat, D.J. (2005).B

enzodiazepines and hypnotics in psychiatry. TheCarlatReport on PsychiatricTreatment, 3(9),1-6.

Carlat, D.J. (2006). Medication treatment of anxiety. TheCarlat Report onPsychiatricTreatment, 4(3),1-6.

Carlat, D.J. (2006). Treating substance abuse. TheCarlat Report on PsychiatricTreatment, 4(6),1-6.

Fuller, M. A., & Sajatovic, M. (2005). PsychotropicDrug Information Handbook, (5th

ed.).Hudson, OH: Lexi-Comp.Keltner, N. L., & Folks, D. G. (2005). Psychotropicdrugs. St. Louis: Elsevier Mosby.Sadock, B. J., & Sadock, V. A. (2003). Kaplan & SadocksSynopsis ofPsychiatry,

(9thed.). Philadelphia: Lippincott Williams & Wilkins.Schatzberg, A. F., Cole, J. O., & DeBattista, C. (2005). ManualofClinical

Psychopharmacology, (5thed.). Washington, D.C.: American Psychiatric Press.Shader, R. I. (2003). Manualofpsychiatrictherapeutics, (3rded.).Philadelphia:

Lippincott Williams & Wilkins.Shiloh, R., Nutt, D., & Weizman, A. (2001). Essentialsin clinicalpsychiatric

pharmacotherapy.London: Martin Dunitz.Stahl, S. M. (2005). EssentialPsychopharmacology: The prescribers guide.

Cambridge: Cambridge University Press.

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