Post on 22-Dec-2015
Anti-depressants
• Depression is considered to be due to functional deficit of neurotransmitters like norepinephrine and / or serotonin.
• Antidepressants act by increasing the concentration of neurotransmitters norepinephrine and / or serotonin in the brain.
Anti-depressants
Drugs used in depression are :• Tricyclic Antidepressants (TCA).• Selective Serotonin Reuptake
Inhibitors (SSRI).• Atypical Antidepressants.• MAO-A inhibitors.
Anti-depressants
TCA : NE / 5-HT reuptake inhibitors : • Tertiary amines : Block reuptake of 5-HT
(serotonin) to a greater extent than NE.
Amitriptyline, Imipramine, Clomipramine• Secondary amines : Block the reuptake of
NE more than serotonin.
Desipramine, Nortriptyline, Amoxapine
Anti-depressants TCA
Anti-depressants
Adverse effects of TCA : • Antimuscarinic effects – dry mouth, blurred
vision and urinary retention.• Alpha-1 blocker – Hypotension. • Histamine -1 blocker – Weight gain. • Arrhythmia.• Seizures.• Induction of mania.
Anti-depressants TCATCA block α-1, muscarinic and histamine -1 receptors.
Anti-depressantsTCA Sedation Antimuscarinic
Hypotension
Imipramine(Tofranil)
++ +++ +++
Clomipramine(Anafranil)
+++ +++ +++
Amitriptyline(Elavil)
+++ +++ +++
Desipramine(Norpramin)
+ + +
Nortriptyline(Pamelor)
+ + +
Amoxapine* (Ascendin)
+ + +
Anti-depressants
Drug interactions of TCA : • Hypertensive crises when given with MAO
Inhibitors.• Serotonin syndrome with SSRI and MAO
Inhibitors.
Anti-depressants
SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI):
• Fluoxetine (Prozac)
• Fluvoxamine (Luvox)
• Sertraline (Zoloft)
• Paroxetine (Paxil)
• Citalopram (Celexa)
• Escitalopram (Lexapro)
SSRI GI effects Sexual effects Agitation
Fluoxetine (Prozac)
++ +++ +++
Sertraline (Zoloft)
+++ +++ +
Paroxetine (Paxil)
++ +++ +/-
Fluvoxamine (Luvox)
++ +++ +/-
Citalopram (Celexa)
++ +++ +/-
Escitalopram (Lexapro)
++ +++ +/-
Anti-depressants
Adverse effects of SSRI: • Nausea.• Insomnia.• Sexual dysfunction.• Suicidal ideation• Weight loss initially but regained after 12
months.• Induction of mania/hypomania.
Anti-depressants
Drug Interactions of SSRI:• Most SSRI are inhibitors of cytochrome
P 450 and can ↑ levels of TCA.• One major contraindication of SSRI is the
concomitant use of MAOI. This is likely to cause severe serotonin syndrome.
• Serotonin syndrome characterized by restlessness, tremor, myoclonus, ↑↑ temperature and death.
Anti-depressants
SEROTONIN / NOR EPINEPHRINE REUPTAKE INHIBITORS : (SNRI):
Venlafaxine (Effexor):• It is a serotonin and NE reuptake inhibitor in
a dose dependent manner.• It does not block muscarinic, adrenergic, or
histaminic receptors.• It is used for the treatment of depression and
anxiety disorders.• Adverse effects includes nausea, sexual
dysfunction, hypertension, suicidal thoughts.
Anti-depressants
SEROTONIN / NOR EPINEPHRINE REUPTAKE INHIBITORS : ( SNRI ) :
Duloxetine (Cymbalta):• Used in major depression, anxiety and also
diabetic neuropathic pain.• It causes nausea and ↑ risk of suicide.
Anti-depressants
ATYPICAL ANTIDEPRESSANTS:Bupropion (Wellbutrin):• It is an inhibitor of reuptake of NE and
dopamine.• Used in ADHD and adjunct therapy for
cessation of smoking.• No weight gain and sexual dysfunction• Very less risk for “switching” to
mania/hypomania.• It causes seizures at high dose.
Anti-depressants
ATYPICAL ANTIDEPRESSANTS:
Mirtazapine (Remeron) :• It enhances the noradrenergic
transmission by blocking presynaptic α - 2 receptors
• It is a potent anti-histaminic with greater sedating effects and weight gain.
Anti-depressants
ATYPICAL ANTIDEPRESSANTS:
Trazodone (Desyrel), Nefazodone (Serzone)• These act mainly by blocking 5-HT-2A
receptors.• Trazodone causes sedation and priapism.• Nefazodone can cause serious hepatic
injury.
Anti-depressants
MAO INHIBITORS :
Phenelzine (Nardil), Tranylcypromine (Parnate), Moclobemide.
• MAO inhibitors are useful in atypical depression.
• MAO-A inhibitors are used when all other antidepressants are not useful and ECT refused.
MAO-Inhibitors
Anti-depressants
MAO INHIBITORS : Adverse effects :
Phenelzine, Tranylcypromine• The most common adverse effects of MAO
inhibitors is postural hypotension.• Anti-cholinergic side effects like dry mouth
are less common compared with TCA.• Impotence and anorgasmia are noted with
MAO inhibitors.
Anti-depressants
MAO INHIBITORS:Interactions:• MAO Inhibitors interact with tyramine –
dangerously leading to hypertensive crisis – cheese reaction.
• Avoid Cheese, Wine, Beer, Pickled fish, Brewer’s yeast, Fava beans, Beef, Chicken liver.
• Avoid sympathomimmetic drugs like phenylephrine.
Anti-depressantsSelegiline (Emsam):• It is the first MAO inhibitor in transdermal patch
form used for major depression.• It can be used without the dangers of dietary
interactions associated with oral MAOI.
St. John’s Wort : • This herbal medication is effective and safe for
mild or moderate depression.• The active ingredient is hypercium.• It inhibits MAO and also appears to block the
reuptake of serotonin.
Anti-depressants
Anti-depressant effect seen after 2-4 weeks
Anti-depressants
Uses of Antidepressants:• Enuresis – TCA • ADHD – TCA • Anxiety disorders like panic / phobia and
bulimia nervosa – SSRI • OCD – SSRI / Clomipramine• Neuropathic pain – TCA
SeizuresHypotension
Anticholinergic
SedationCardiac effects
Sexual effects
TCA +++ +++ +++ +++ +++ +++
SSRI + - - Insomnia - +++
Bupropion ++ - - Psychosis - -
MAOI + ++ +++ Insomnia - +++
Anti-depressants
Conclusions:
• SSRIs are safe and effective for the treatment of major depression.
• SSRIs are first line for chronic treatment of anxiety disorders including OCD.
• MAO inhibitors are effective for the treatment of atypical depression.
• Psychotic depressed patients usually requires ECT.
Bipolar disorder
Mood stabilizers
• LITHIUM is a monovalent cation• Lithium has a narrow therapeutic index• Lithium is used for prevention and the
treatment of bipolar disorder. • Valproate and carbamazepine are the
alternatives for the BPD.• Lamotrigine also acts as a mood stabilizer.
Mood stabilizers
MECHANISM OF ACTION: LITHIUM• Inhibits inositol monophosphatase and thus
interfere with phosphatidyl inositol pathways
• Decrease the recycling of inositol in the neuronal cell membrane.
• Decrease the cAMP.
Mood stabilizers
PHARMACOKINETICS OF LITHIUM:• Orally absorbed. • Slow onset. • Plasma levels ~ 1 meq / liter.• Thiazides, NSAIDS enhances lithium
toxicity.
Mood stabilizers
Adverse effects of Lithium :• Tremors, weight gain, acne.• Polyuria and polydipsia – nephrogenic
diabetes insipidus – Amiloride.• Hypothyroidism.• Seizures and arrhythmia.• Teratogenicity - Ebstein’s malformation.
Mood stabilizers
• Symbyax is a combination of olanzapine and fluoxetine for the treatment of bipolar depression.
• Aripiprazole (Abilify) is approved for the treatment of acute manic and mixed episodes associated with bipolar disorder.