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SELECTIVE SEROTONIN RE-UPTAKE
INHIBITORS
GENERAL INFORMATION
Antidepressant of choice for new prescriptions Safer in overdose :. much more popular than TCAs Uses: depression, OCD, panic disorder, social anxiety, PTSD, Bulemia, social phobia, migraines Drug interactions are very common and important: most are potent P450 inhibitors Tremors, headaches, nervousness, anxiety, insomnia, anorexia, suicidal ideation, depression, worsening of mood swings EPS including akathisia and dystonia can occur PHARMACOLOGY and PATHOPHYSIOLOGY
Specific inhibitors of Seritonin re-uptake thus increase the amount of seritonin in the synapse Anti-depressant effect may actually be mediated through reduction of dopaminergic release There is a complex relationship between seritonin and dopamine (thus overlap between seritonin syndrome and neuroleptic malignant syndrome) Do NOT have significant effects on GABA, Na channels, or adrenergic re-uptake CLINICAL MANIFESTATIONs
Seizures: all can cause but only citalopram (Celexa) is common (can be delayed) QT prolongation: all can cause but only citalopram (Celexa) is common Seizure and QT prolongation in dose related manner Typically occur with > 600 mg of citalopram or serum levels 40Xs expected Parent and metabolite of drug are implicated Carelfully monitor for QT prolongation and seizures MANAGMENT
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Lavage generally not indicated as they are rarely life-threatening ATYPICAL ANTIDEPRESSANTS
EFFEXOR = SNRI: Serotonin and NE Reuptake Inhibitor
Less drug interactions than SSRIs b/c no enzyme inhibition and no protein binding Sympathomimetic effects related to increased NE: HTN, tachycardia, mydriasis, diaphoresis, CNS alteration common: mild agitation to decreasing LOC Wide QRS and ventricular tachycardia have rarely occurred Seizures have rarely ocurred (think of serotonin syndrome though) Observe 4-6hrs before “medical clearance” TRAZADONE = SARI: Serotonin-2 Antagonists and Reuptake Inhibitors
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Desyrel (trazadone); also Serzone (nefazodone) Peripheral alpha1 antagonism thus orthostatic hypotension Adverse effects: sedation, dizziness, orthostatic hypotension, priaprism Serious toxicity unlikely < 2g ingestion PE: decreased LOC, ataxia, seizures, orthostasis (responds to fluids) Fluids +/- norepinephrine for hypotension Medically cleared if asymptomatic after 6hrs WELLBUTRYN = NDRI: Norepinephrine and Dopamine Reuptake Inhibitors
Useful for: psychomotor retardation, hypersomnia, cognitive slowing, inattension (ADHD), cravings (smoking cessation) Side effects: anxiety, insomnia, H/As, GI, sz Seizures are main problem
Contraindicated if hx of seizures or bulemic Seizures caused by metabolite (hydroxybuproprion) thus can be delayed Toxicity can occur at maximal recommended dose of 450 mg/d Significant toxicity usu occurs w/ > 5mg/Kg Tacchycardia, lethargy, tremor, generalized seizure, confusion ECG: sinus tach, can cause QT prolongation but not common SEIZURES common up to 10 hrs a/f OD (especially if delayed release) BZD first line, phenobarb 2nd line, phenytoin 3rd line Observe for 6 hrs and d/c if asymptomatic Admit for seizures, sinus tach, lethargy, symptomatic a/f 8hr SEROTONIN SYNDROME
GENERAL INFORMATION
Also called serotonin behavioral or hyperactivity syndrome First described with patients on MAOIs that were given other seritonergic drugs Ingestion of MAO-I is not neccessary for development of this syndrome Pathophysiology not well understood but involves excessive stimulation of seritonin receptors (specifically the 5-HT1A receptor) SSRIs (prozac, paxil, fluvox, celexa, zoloft) DIFFERENTIAL DIAGNOSIS OF SERITONIN SYNDROME
Note close relationship b/w seritonin and dopamine Both have Cognitive, Autonomic, and Neuromuscular features Seritonin syndrome develops sooner than NMS NMS lasts longer than seritonin syndrome (SS usu < 24hrs) Lead pipe rigidity with NMS versus hyperreflexia with SS Can be hyperreflexic, seizure, clonus due to central alpha effects Usually not pronounced hyperreflexia, clonus KEY FEATURES
Definition = cognitive change + autonomic alteration + neuromuscular activity Other features reported: rhabdomyolysis, DIC, ARF, hepatic failure, lactic acidosis, ARDS COGNITIVE
- agitation
- confusion
- delirium
- hypomania
- euphoria
- insomnia
AUTONOMIC ALTERATION
- tachycardia, hypertension
- fever, shivering, diaphoresis
- arrythmias, tachypnea, abdo cramping
- mydriasis
NEUROMUSCULAR ACTIVITY
- tremor, nystamus
- hyper-reflexia
- clonus, myoclonus
- ataxia, incoordination
- seizures
STERNBACH’S CRITERIA
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(i) Addition or increased dose of a known seritonergic agent + at least three of the CAN features (ii) Other etiologies excluded (infectious, metabolic, substance abuse, withdrawl, stimulants) (iii) No neuroleptics that have been started or increased prior to onset of symptoms SEVERITY
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MILD: diaphoresis, incr temp and BP, dilated pupils, hyperreflexia MOD: mydriasis, slurred speach, ankle clonus, diaphoresis SEVERE: marked CNS changes, marked autonomic instability, INCREASED temp TREATMENT
Temp: aggressive external cooling maneuvers (antipyretics will NOT work); check temps q1hr; paralysis if necessary (increased temp from muscular activity) Antihistamine with non-specific antagonism of 5-HT1A and 5-HT2 receptors Dose: 4 mg q2-4 -8 hrs prn to max 0.5 mg/kg/day Not know whether it really works: cooling and BZDs are more important Other: Dantrolene: use if temp and rigid, not specifically studied in S.S.,Chlorpromazine: don’t use

Source: http://www.remergs.com/WEBPAGE%20Notes/Toxicology/SSRIs%20and%20Atypical%20Antidepressants.pdf