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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 l.jpg

Julie Kennedy

Antidepressants


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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


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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


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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)


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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


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Targets of antidepressants self-injury

Serotonin

  • Monoamine neurotransmitter receptors

  • Monoamine reuptake transporters

  • Glutamate receptors (NMDA, mGluRs)

  • GABA receptors, transporters

Norepinepherine

Dopamine

Glutamate

GABA


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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


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Tricyclic antidepressants agent)

  • Three fused rings (6,7,6 carbons)

  • Inhibit serotonin and norepinepherine reuptake

  • Developed from antihistamines

  • Common side effects: dry mouth, constipation, dizziness

Desipramie

Imipramine


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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


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Theories for 2-3 week delay in effectivness agent)

  • 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


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Common SSRIs agent)

  • 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


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Serotonin-Norepinepherine reuptake inhibitors agent)

  • 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


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Norepinepherine reuptake inhibitors agent)

  • Introduced in 1970s to increase selectivity

  • Reboxetine: most effective at improving social functioning

  • Side effects: blurred vision, hypotension tremors, headache, urinary hesitancy


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Dopamine agonists agent)

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

(Dopamine)


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Lithium agent)

  • 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)


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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


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Future of anitdepressants antidepressants for at lease 6 weeks

  • 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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