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
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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
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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
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Sexual dysfunction
Weight gain
Serotonin syndrome: 2 – 72 hours
Withdrawal Syndrome
Teen suicide?
My experience with patients:
– “feel flat,” “feel unresponsive”
– Disturbing dreams
Agents
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Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Fluvoxamine (Luvox)
Citalopram (Celexa)
Escitalopram (Lexapro) (left hand of
citalopram)
Teaching Points
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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
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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
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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
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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
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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!!!!!!