Antidepressants, Anxiolytics, and Sedative/Hypnotics

Antidepressants

• Tricyclic Antidepressants (TCAs)

• Monoamine Oxidase Inhibitors (MAOIs)

• Selective Serotonin Reuptake Inhibitors (SSRIs)

• Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

• Atypical antidepressants

• Atypical antipsychotics

Depression

• Depressed mood, loss of pleasure or interest in usual activities

• Sustained over time• Subtypes

– Major depression– Clinical depression– Subclinical depression– Post-partum– Bereavement

Depression

• Every patient in the hospital needs to have depression addressed– Loss of functionality– Loss of youth/feeling of control– Chronic illness– Altered sleep and exercise patterns\– Altered role

Depression Treatment

• Cognitive therapy

• Behavioral therapy (exercise, art, etc.)

• ECT

• Pharmacology– Older protocol: treat major depression 6 – 12

months– Newer: long term or lifelong therapy– Distinguish: situational/transient depression

TCAs

• Old drugs, cheap

• Multiple actions unsure– Inhibition of Norepinephrine & Serotonin reuptake

• Multiple side effects

• Not effective for depression except at high doses

• May be toxic before becomes effective

• Often used as adjunct for sleep and pain

Adverse Effects

• Orthostatic hypotension

• Anticholinergic effects

• Diaphoresis

• Sedation

• Cardiac toxicity

• Seizures

• Hypomania

TCA Treatment

• Must start low avoid toxicity– Takes several weeks to achieve effect– Starting high does not decrease time

• Selecting a drug– Most are dosed once daily, usually HS– Choosing your side effects

• More sedating drugs for patients with insomnia, etc.

– Common agents: amitriptyline, nortriptyline, imipramine

MAOIs

• Older drugs• Relatively effective, but high toxicity

– Especially drug and food interactions

• Considered third line therapy• Hypertensive crisis

– When using MAOIs, avoid• Avocadoes, cheese, wine, beer, soups, soy sauce,

chocolate, caffeine, smoked foods

• Yeah… no wonder they’re depressed

• Linezolid (Zyvox): MAOI features

SSRIs

• Relatively new (1987)

• Most prescribed class for depression

• Blocks reuptake of serotonin only– Take 2 – 3 weeks for therapeutic effect

• Uses:– Depression– Anxiety– Social phobia, obsessive-compulsive, PDD

Adverse Effects

• Sexual dysfunction

• Weight gain

• Serotonin syndrome: 2 – 72 hours

• Withdrawal Syndrome

• Teen suicide?

• My experience with patients:– “feel flat,” “feel unresponsive”– Disturbing dreams

Agents

• Fluoxetine (Prozac)

• Sertraline (Zoloft)

• Paroxetine (Paxil)

• Fluvoxamine (Luvox)

• Citalopram (Celexa)

• Escitalopram (Lexapro) (left hand of citalopram)

Teaching Points

• Therapeutic delay

• Warning signs of Serotonin Syndrome

• Withdrawal syndrome

• Sexual side effects

SNRIs

• Venlafaxine (Effexor) – NE & serotonin reuptake inhibitor (weak dopamine); causes mild excitation

• Duloxetine (Cymbalta)

Atypical Antidepressants

• Bupoprion (Wellbutrin)

• Nefazadone (Serzone) – multiple effects

• Mirtazapine (Remeron) – new class of drug; increased release of NE and serotonin

Bupoprion (Wellbutrin)

• Unclear action, but definitely blocks something with Dopamine

• May increase sexual desire

• May cause excitation

• Dopamine associated with addictive behaviors– Bupoprion marketed for smoking cessation

(Zyban)– Also may help concentration ADD

Atypical Antipsychotics

• Are not used for depression alone– Potentiate other antidepressant drugs– Used for depression with psychotic features

• Common agents– Clozapine (Clozaril)– Risperidone (Risperdal)– Olanzapine (Zyprexa)– Quetiapine (Seroquel)

Sedative-Hypnotics

• Benzodiazepines

• Benzo-like

• Barbiturates

• Miscellaneous

Benzodiazepines

• Safer and lower abuse potential that other CNS depressants (barbiturates)

• Mechanism– Potentiate GABA (CNS neurotransmitter)– Bind to GABA-chloride gate receptors and

enhance the natural action of GABA– Finite action

• All are controlled substances

Benzodiazepines

• Effects– CNS

• Reduce anxiety• Promote sleep• Muscle relaxation• Anterograde amnesia

– CV: PO none; IV hypotension, cardiac arrest– Resp: weak depressants alone

Kinetics

• Most well absorbed PO

• Metabolism– Most have active metabolites– Duration is wildly different among agents– Example

• Flurazepam: 2-3 hour half-life; metabolite 50 hours

Benzo Uses

• Anxiety• Insomnia• Seizure• Muscle Spasm• Alcohol withdrawal (DT prevention)• Panic Disorder• Surgery

– Induction of anesthesia– Conscious sedation

Adverse Effects

• CNS: drowsy, lightheaded, concentration, MVA

• Amnesia

• Paradoxical effects

• Resp depression

• Abuse

• Don’t use in pregnant women

Common Benzos

• Diazepam (Valium)

• Lorazapam (Ativan)

• Alprazolam (Xanax)

• Clonazepam (Klonopin)

• Chlordiazepoxide (Librium)

• Temazepam (Restoril)

• Midazolam (Versed) – conscious sedation

Benzo-like

• Unrelated to Benzo chemical structure, but upregulate GABA in a similar manner

• Schedule IV drugs– Zolpidem (Ambien)

• Middle of the night confusion

– Zaleplon (Sonata)• Better for falling asleep, not staying asleep

Barbiturates

• Bind to GABA-chloride receptor– Directly activate receptor– Enhance GABA’s natural action– No ceiling on effect

• Highly addictive

• Therapeutic uses for – Seizure – Anesthesia induction

• Common: Phenobarbital

Other Sedative-Hypnotics

• Antidepressants– Amitriptyline (Elavil)– Trazadone

• 1st generation antihistamine– Diphenhydramine (Benadryl, Nytol, Sominex)– Doxylamine (Unisom)– Hydroxyzine (Atarax)

Anxiety

• Benzos, SSRIs, others– Generalized Anxiety Disorder– Situational anxiety

• SSRIs– Panic disorder– Obsessive-Compulsive D/O– Social anxiety– PTSD

Other Anxiolytics

• Buspirone (Buspar)– No sedation– No abuse potential– No interaction with ETOH– BUT, develops slowly: at least a week– Takes several to reach full potential– Used for short term therapy (up to a year)

• Beta blockers– Primarily for performance/test anxiety

Vitamin H:The Abused Antipsychotic

• Haloperidol (Haldol)– Often prescribed by physicians for inpatient

“agitation”– “ICU psychosis”– Haldol is not a sedative. Should not be used

as either a sedative nor anxiolytic– If giving it more than twice a day

• CALL THE PHYSICIAN AND GET ANOTHER DRUG ORDERED!!!!!!