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SSRIs
citalopram (Celexa), escitalopram (Lexapro),fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine(Paxil), sertraline (Zoloft)
SSRIs inhibit 5HT reuptake butdo not act on NE or dopamine
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Serotonin syndrome
increased levels of 5HT in CNS --> Altered mental status, agitation, fever, hypotension,ataxia, hyperreflexia, myoclonus
Concern with combining any agents that increase CNS 5HT levels (SSRIs, MAOIs, TCAs, psycho stimulants,dopamine agonists, buspirone, sumatriptan, meperidine, dextromethorphan)
and
MAOI + SSRI, dextromethorphan,meperidine, TCAs, trazodone, lithium,
or
SSRI + another SSRI venlafaxine, dextromethorphan,buspirone, carbamazepine, lithium, mirtazapine, tramadol, nefazodone, sumatriptan, or “ecstasy”
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Discontinuation syndrome in SSRIs
Transient dizziness and vertigo, lethargy, paresthesias(paroxetine), nausea, vivid dreams, irritability
Treat by tapering dose
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High-yield facts about SSRIs
- Fluoxetine: longest half-life and active metabolite with longest half-life, side effects include reduced appetite
- Fluoxetine and fluvoxamine: best profile inregard to sexual side effects
- Sertraline: worst profile in regard to sexual side effects, most potent blocker of dopamine transporters, has active metabolite with short half-life
Fluvoxamine and paroxetine: no active metabolites, more likely to cause discontinuation syndrome with abrupt withdrawal of drug
Citalopram: most selective for 5HT
Paroxetine: most potent SSRI, side effects include weight gain and somnolence
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MAOIs
- isocarboxazid (Marplan),
- phenelzine (Nardil),
- tranylcypromine (Parnate)
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TCAs and Metabolism
TCAs + alcohol, carbamazepine, phenytoin, cigarette smoking --> increased metabolism of TCAs sub therapeutic levels of TCAs
- TCA + neuroleptics, SSRIs (especially paroxetine and fluoxetine), cimetidine methylphenidate (Ritalin),quinidine, thyroid medications --> decreased metabolism of
- TCAs -->potentially toxic levels of TCAs
Nortriptyline: therapeutic window from 50 to 150 ng/mL, less effective at both very high and very low doses
Amitriptyline: therapeutic range is 75 to 175 ng/mL
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Mixed-mechanism antidepressants
bupropion, duloxetine,mirtazapine, nefazodone, trazodone, venlafaxine
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Bupropion (Wellbutrin)
DA/NE reuptake inhibitor
Indications: smoking cessation, MDD, adult ADHD
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Duloxetine (Cymbalta)
5HT/NE reuptake inhibitor
Indications: MDD, diabetic peripheral neuropathic pain
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Mirtazapine (Remeron):
enhances NE and 5HT release via α2-antagonism, potent histamine antagonist, antagonist of 5HT2, 5HT3 receptors
Indications: MDD, improves sleep/appetite
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Nefazodone
inhibitor of serotonin uptake and weakly of NE reuptake, antagonist of 5HT2A, may selectively activate 5HT1A
Indications: MDD
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Trazodone (Desyrel)
blocks 5HT2 receptor, weak inhibitor of 5HT reuptake
Indications: MDD, insomnia
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Venlafaxine (Effexor):
inhibits 5HT reuptake at lowdoses, NE/DA at higher doses
Indications: MDD, GAD, social anxiety disorder
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Atypicals Antipsychotics:
clozapine, risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone
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Atypical Antipsychotics
Aripiprazole (Abilify): partial agonist D2, 5HT1A receptors and antagonist at 5HT2A receptors
Clozapine (Clozaril): low potency, EPS/TD nearly absent, good with positive and negative symptoms, Warning—agranulocytosis potential, seizures
Quetiapine (Seroquel): low potency, few EPS, less sexual dysfunction, no prolactin increase
Olanzapine (Zyprexa): medium/high potency, fewEPS, high weight gain
Risperidone (Risperdal): high potency, few EPS,can increase prolactin, more sexual dysfunction
- Ziprasidone (Geodon): good for positive and negativesymptoms, improves cognition and depression,low EPS, not associated with weight gain
- Warning—can lead to QT prolongation
Indications:Psychotic disorders, schizophrenia, mood disorderwith psychotic features, delirium, acute mania, aggressive behaviors, psychosis due tomedical condition or substances
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Akathisia
(subjective feelings of anxiety, tension, agitation): treat by lowering dose of antipsychotic, try β-blocker, clonidine, amantadine, or benzodiazepine
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Preferred benzodiazepines for the elderly
oxazepam,lorazepam, temazepam (“out the liver”)
- 1) have no active metabolites
- 2) Relatively short acting
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Buspirone (BuSpar)
- -Other anxiolytics, sedative-hypnotics
- - Used for generalized anxiety disorder: effects seenafter 1 to 2 weeks
- Relatively nonsedating, no abuse potential
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Clinical use in Parkinson’s disease: ECT
ECT may improve both mood and motor symptoms of patients with advanced Parkinson’s disease, but effects may be short lived from days to weeks to 6 months, according to variousstudies
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Possible contraindications of ECT:
- -active pulmonary infection,
- -recent MI,
- -unstable CAD,
- -CHF,
- -uncontrolled hypertension,
- -space-occupying brain lesion,
- -increased ICP,
- -recent cerebrovascular accident,
- -history of anesthesia complications,
- -seizure,
- -reflux,
- -aneurysms,
- -venous thrombosis,
- -recent bone fracture (especiallycervical spine)
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Adverse effects of ECT
- -brief episode of hypotension or hypertension,
- -bradyarrhythmia or tachyarrhythmia,
- -prolonged seizures,
- -prolonged apnea (due to pseudocholinesterase deficiency),
- -postictal confusion,
- -headache,
- -nausea,
- -muscle pain,
- -memory impairment (retrograde amnesia forshort time surrounding hospitalization)
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Lithium:
inhibits inositol-1-phosphatase
Indications: mania, augmentation of antidepressants, prophylaxis of mania/depression,schizoaffective disorder, aggression, impulsivity
Concerns: thyroid/kidney, pregnancy (Ebstein’sanomaly)
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Valproate
enhances GABA Indications: mania, augmentation of antidepressants, alcohol withdrawal states, rapid cycling
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Neurasthenia
Neurasthenia is a psycho-pathological term first used by George Miller Beard in 1869[1] to denote a condition with symptoms of fatigue, anxiety, headache,neuralgia and depressed mood.
Neurasthenia is currently a diagnosis in the World Health Organization's International Classification of Diseases (and in the Chinese Classification of Mental Disorders, translated as 神经衰弱). However, it is no longer included as a diagnosis in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders.
Americans were said to be particularly prone to neurasthenia, which resulted in the nickname "Americanitis"[2] (popularized by William James). Today, the condition is still commonly diagnosed in Asia.
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Amphetamine
introduced in 1930s, dextroamphetamine (Dexedrine), combination of amphetamine and dextroamphetamine (Adderall)
- Clinical use:
- 1) Narcolepsy and other sleep disorders, attentiondeficit/ hyperactivity disorder in children, obesity
- 2) Has also been used for depression by augmenting antidepressant effects, neurasthenia, AIDS dementia, encephalopathy from brain injury
- b. Mechanism of action
- 1) Causes direct release of dopamine and NE from neurons
- 2) Blocks reuptake of catecholamines
- 3) Peak plasma levels in 1 to 3 hoursc.
Effects: CNS stimulation, appetite suppression, vasoconstriction, hypothermia, tolerance can developd.
Adverse effects: stomach pain, anxiety, irritability, insomnia, tachycardia, arrhythmias, dysphoria, may worsen tics, psychosis, paranoia, delusions, delirium, seizurese.
Monitor: blood pressure and pulse initially and after changes in dose, weight and height initially and several times annually
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Methylphenidate (Concerta, Ritalin):
related toamphetamine, but milder stimulant (little or no abusepotential)
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Modafinil
Modafinil (Provigil): novel stimulant for narcolepsy
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