Antidepressants, Anxiolytics, and Sedative/Hypnotics

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Antidepressants, Anxiolytics, and
Sedative/Hypnotics
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Antidepressants

• Tricyclic Antidepressants (TCAs)
• Monoamine Oxidase Inhibitors (MAOIs)
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Serotonin Norepinephrine Reuptake Inhibitors
  (SNRIs)
• Atypical antidepressants
• Atypical antipsychotics

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Depression

• Depressed mood, loss of pleasure or interest in
  usual activities
• Sustained over time
• Subtypes
• Major depression
• Clinical depression
• Subclinical depression
• Post-partum
• Bereavement

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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

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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

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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

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Adverse Effects

• Orthostatic hypotension
• Anticholinergic effects
• Diaphoresis
• Sedation
• Cardiac toxicity
• Seizures
• Hypomania

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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

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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 theyre depressed
• Linezolid (Zyvox) MAOI features

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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

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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

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Agents

• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Paroxetine (Paxil)
• Fluvoxamine (Luvox)
• Citalopram (Celexa)
• Escitalopram (Lexapro) (left hand of citalopram)

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Teaching Points

• Therapeutic delay
• Warning signs of Serotonin Syndrome
• Withdrawal syndrome
• Sexual side effects

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SNRIs

• Venlafaxine (Effexor) NE serotonin reuptake
  inhibitor (weak dopamine) causes mild excitation
• Duloxetine (Cymbalta)

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Atypical Antidepressants

• Bupoprion (Wellbutrin)
• Nefazadone (Serzone) multiple effects
• Mirtazapine (Remeron) new class of drug
  increased release of NE and serotonin

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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

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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)

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Sedative-Hypnotics

• Benzodiazepines
• Benzo-like
• Barbiturates
• Miscellaneous

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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

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Benzodiazepines

• Effects
• CNS
• Reduce anxiety
• Promote sleep
• Muscle relaxation
• Anterograde amnesia
• CV PO none IV hypotension, cardiac arrest
• Resp weak depressants alone

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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

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Benzo Uses

• Anxiety
• Insomnia
• Seizure
• Muscle Spasm
• Alcohol withdrawal (DT prevention)
• Panic Disorder
• Surgery
• Induction of anesthesia
• Conscious sedation

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Adverse Effects

• CNS drowsy, lightheaded, concentration, MVA
• Amnesia
• Paradoxical effects
• Resp depression
• Abuse
• Dont use in pregnant women

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Common Benzos

• Diazepam (Valium)
• Lorazapam (Ativan)
• Alprazolam (Xanax)
• Clonazepam (Klonopin)
• Chlordiazepoxide (Librium)
• Temazepam (Restoril)
• Midazolam (Versed) conscious sedation

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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

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Barbiturates

• Bind to GABA-chloride receptor
• Directly activate receptor
• Enhance GABAs natural action
• No ceiling on effect
• Highly addictive
• Therapeutic uses for
• Seizure
• Anesthesia induction
• Common Phenobarbital

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Other Sedative-Hypnotics

• Antidepressants
• Amitriptyline (Elavil)
• Trazadone
• 1st generation antihistamine
• Diphenhydramine (Benadryl, Nytol, Sominex)
• Doxylamine (Unisom)
• Hydroxyzine (Atarax)

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Anxiety

• Benzos, SSRIs, others
• Generalized Anxiety Disorder
• Situational anxiety
• SSRIs
• Panic disorder
• Obsessive-Compulsive D/O
• Social anxiety
• PTSD

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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

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Vitamin HThe 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!!!!!!