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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!!!!!!