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Julie Kennedy

Julie Kennedy. Antidepressants. Physiological effects. Symptoms. Anhedonia- loss of interest in everyday activites Despondent mood Altered sleep patterns Changes in weight/appetite Persistent feelings of guilt Morbid thoughts Agitation Inability to concentrate

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Julie Kennedy

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  1. Julie Kennedy Antidepressants

  2. Physiological effects Symptoms • Anhedonia- loss of interest in everyday activites • Despondent mood • Altered sleep patterns • Changes in weight/appetite • Persistent feelings of guilt • Morbid thoughts • Agitation • Inability to concentrate • Loss of executive memory • Indecisiveness • Depleted monoamine neurotransmitters: serotonin, norepinepherine, dopamine • Degeneration of neurons and synaptic connectivity • Decreased GABA levels • Imbalanced HPT (hypothalamic-pituitary-thyroid) axis • Increased cytokine levels

  3. DSM-IV Major depressive disorder: 2 weeks depressed mood or loss of interest accompanied by 4 additional symptoms Dysthymic disorder: 2 yrs depressed mood for more days than not ICD-10 Mild to moderate depression: common symptoms + functional impairment Severe depression: physical symptoms Systems of diagnosis

  4. Treatments available • Antidepressant drugs (SSRIs, TCAs, MAOIs) • Counseling (Cognitive therapy, interpersonal psychotherapy, non-directive counseling, befriending, exercise, problem solving therapy) • Natural supplements (St Johns Wort) • Electroconvulsive therapy (ECT)

  5. Anaesthetisia, muscle relaxant administered to avoid self-injury Electrical current passed through brain to induce seizure Unknown method of action (thought to involve NTs) Mainly for drug resistant depressed patients 10% inpatients receive ECT 70% of all patients receiving ECT are women Older patients more common More common in Asia, S. America, Africa--may be used without anaesthesia & muscle relaxants Electric shock treatment

  6. Targets of antidepressants Serotonin • Monoamine neurotransmitter receptors • Monoamine reuptake transporters • Glutamate receptors (NMDA, mGluRs) • GABA receptors, transporters Norepinepherine Dopamine Glutamate GABA

  7. 1st antidepressants introduced (iproniazid, antitubercular agent) Inhibit degradation of catecholamine to aldehydes Mechanis of MAOI action not well understood More likely to have side effects Used more commonly for atypical depression Interaction with tyramine (cheese)--MAOIs enable its systemic circulation Monoamine Oxidase Inhibitors

  8. Tricyclic antidepressants • Three fused rings (6,7,6 carbons) • Inhibit serotonin and norepinepherine reuptake • Developed from antihistamines • Common side effects: dry mouth, constipation, dizziness Desipramie Imipramine

  9. Mode of action remains largely inconclusive • Direct-to-consumer marketing • Sales exceed $17 billion worldwide in 2003 • Interference with MDMA, cocaine, TCAs • May intitially increase suicide risk Selective Serotonin Reuptake Inhibitors • Similar efficacy with Tricyclic’s, but lower side effects • Introduced in the 1980s-90s • Block serotonin uptake @ presynaptic 5-HT transporter • Act on 4-TM ion channel receptors and 7-TM GCPRs

  10. Theories for 2-3 week delay in effectivness • Quickly increase serotonin concentraion, which inhibits 5-HT firing, autorecptors become desensitized after prolonged SSRI exposure • Feedback regulation at 5-HT receptors requiring chronic administration to sustain therapeutic sertonin levels • Need for alterations in genetic ∂ and ß-adrenergic receptor expression • Changes in nerve connectivity and neurotrophic factors

  11. Common SSRIs • Fluoxetine (Prozac): best selling antidepressant, 1st SSRI to have real success • Sertraline (Zoloft): 6th best-selling overall med. In the US in 2004 ( >$3 bill.) • Paroxetine (Paxil)” short half-life, controlled release available

  12. Serotonin-Norepinepherine reuptake inhibitors • Even newer, less selective • Faster onset • Venlafaxine (Effexor): 1993, generic 2006 • Duloxetine (Cymbalta): lower risk of relapse • Common side effects: sweating, weightloss, nausea, diarrhea, constipation, vomiting, dry mouth

  13. Norepinepherine reuptake inhibitors • Introduced in 1970s to increase selectivity • Reboxetine: most effective at improving social functioning • Side effects: blurred vision, hypotension tremors, headache, urinary hesitancy

  14. Dopamine agonists • Bupropion (Wellbutrin): blocks reuptake of norepinepherine and dopamine, less risk of side effects, used as an aide to quit smoking (Dopamine)

  15. Lithium • Lithium bicarbonate (Li2CO3) • Most commonly used for bipolar disorder • Mode of action poorly understood, thought to reduce the action of the HPT system • Dosed by augmentation (increasing until desired effects acheived)

  16. Occurs within 3 days of cessation, only occurs after taking antidepressants for at lease 6 weeks Also occurs when switching antidepressants or switching to generic “equivalent” (may be up to 20% different) Flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, hyperarousal Generally resolves itself after 2 weeks Misleadingly termed “withdraw,” since antidepressant are not habit-forming Antidepressant Dis-continuation Syndrome

  17. Future of anitdepressants • Many aspects of both depression and action of antidepressants remain not well understood • Much room for development: increased specificity, decreased side effects, decreased time for onset of action

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