impotant topic in psychiatry

1. Antidepressants,
Anxiolytics,
Hypnotics

2. Antidepressants
Uses:
-Mainly used to treat MDD
-Panic disorder
-PTSD (Post-traumatic stress disorder)
-GAD (Generalized anxiety disorder)
-OCD (obsessive-compulsive disorder)
-PMDD(premenstrual dysphoric disorder)
-Neuropathic pain

3. Pathophysiology of MDD
-Not clearly defined
-Complex interaction between neurotransmitter availability and receptor
regulation and sensitivity
-Disturbance in CNS Serotonin (5-HT) is an important factor
-Other neurotransmitters include norepinephrine (NE), Dopamine (DA),
Glutamate & brain-derived neurotrophic factor (BDNF)
-Monoamine hypothesis: The underlying pathophysiological basis of
depression is a depletion in the levels of serotonin, norepinephrine and/or
dopamine in the CNS.

4. Types of Antidepressants
-SSRI’s (Selective Serotonin Reuptake Inhibitors)
-SNRI’s (Serotonin-Norepinephrine Reuptake Inhibitors)
-NaSSA (Noradrenaline specific Serotonin antidepressant)
-TCA’s (Tricyclic antidepressants)
-5-HT modulators (Hydroxytryptamine)
- Tetracyclics and unicyclics
- MOI (Monamine Oxidase Inhibitors)

5. SSRI’s (Selective Serotonin Reuptake
Inhibitors)
- Primary action is to inhibit the serotonin transporter
- Fluoxetine, sertraline, citalopram, paroxetine, fluvoxamine, escitalopram
- safety in overdose
- relative tolerability
- cost (all are available as generic products)
- CI: Mania
- S/E: -GIT (Nausea, abdominal pain, diarrhoea, constipation, weight loss)
-Autonomic (agitation, tremor, insomnia)
-Sexual dysfunction

6. Fluoxetine
-Dose starting at 20mg daily , up to 60mg daily
-Upon therapy discontinuation, needs to be gradually tapered over 4 -6 months to
minimize withdrawal symptoms
-Indications: OCD, panic disorder, Bulimia nervosa, PTSD, PMDD, childhood
depression
-S/E: Anxiety, agitation, insomnia, nausea, headache, weakness, diarrhoea, dry
mouth
-Contraindicated in breastfeeding
-Peak plasma time: 6-8 hrs
-Half life: 4-6 days (chronic); 1-3 days (acute)

7. Citalopram
-Dose starting at 20mg daily
-May increase to 40mg/daily after at least 1 week
-Doses above 40mg not recommended as it increases risk of QT prolongation
-Top 5 side effects: Dry mouth, nausea, somnolence, insomnia
-Pregnancy category C : use in the 3rd trimester associated with complications in
newborns (PPHN)
-Peak serum time: 1-6 hrs
-Full response may not be seen until 8-12 weeks after initiating treatment
-Half life 24-48 hrs

8. Sertraline
-Dose 50mg to 200mg daily
-Indication: PMDD, OCD,PTSD
-Half life 26-32 hrs
-S/E: GIT disturbances, headache, insomnia, dry mouth

9. SNRI’s (Serotonin-Norepinephrine Reuptake
Inhibitors)
- Work by binding and inhibiting the serotonin (SERT) and
norepinephrine (NET) transporters
- Duloxetine, Venlafaxine, Levomilnacipran

10. NaSSA
(Noradrenaline specific Serotonin
antidepressant)
-Mirtazapine
-Dose 15mg- 45mg daily
-Indications: Insomnia, poor appetite, dysthymia, PTSD, Chronic pain
-S/E: drowsiness, weight gain, increased appetite, dry mouth, postural
hypotension

11. TCA’s (Tricyclic antidepressants)
- Work by binding and inhibiting the serotonin (SERT) and norepinephrine (NET)
transporters
- Indications: depression that is unresponsive to other antidepressants; anxiety
disorders, severe OCD, neuropathic pain, migraine, enuresis
- Poorer tolerability compared with newer agents
- Lethality in overdose
- CI: Cardiac diseases, epilepsy, severe liver dx, mania, prostatic hypertrophy
- S/E: anticholinergic effects( constipation, blurred vision, urinary retention, dry
mouth, dizziness, syncope, sedation); weight gain, hyponatraemia, cardiac
changes(QTc prolongation, tachycardia, heart block)
- Imipramine, Amitriptyline, Doxepin , Desipramine, Nortriptyline, Protriptyline,
Clomipramine, Trimipramine

12. Amitriptyline
-Dose starts at 25mg-50mg po nocte
-Side effects: Constipation, Dry mouth, dizziness, sedation, headache,
weight gain, diarrhoea, urinating less, impotence, decreased libido
-Pregnancy category C
-Peak serum time: 4 hrs
-Half life : 9-27 hrs

13. 5-HT modulators
- Antagonists at the 5-HT2 receptor: trazodone and nefazodone

14. Tetracyclics and Unicyclics
-Bupropion, mirtazapine, amoxapine, vilazodone, and maprotiline
-Have structural similarities and side effects comparable to TCAs,
therefore they are not commonly prescribed in current practice
-Used in MDD that is unresponsive to other agents

15. Monoamine Oxidase Inhibitors
- High risk of toxicity and potentially lethal food and drug interactions
- Used in the treatment of depression unresponsive to other
antidepressants.
- Phenelzine, isocarboxazid, tranylcypromine, selegiline, and
moclobemide
- Irreversible MOI’s interact with food containing tyramine & can lead to a
hypertensive crisis (alcohol, banana skin, bean curds, cheeses, caviar)

16. Serotonin Syndrome
-Hyper-stimulation of the postsynaptic serotonin receptors
-Major area for drug-drug interactions
-Mechanisms: Increased 5-HT production; Increased 5-HT release;
Inhibition of 5-HT metabolism; Stimulation of 5-HT receptors; SSRI’s
overdose
-Drug interactions: Combined SSRI’s; MAO-I, Methamphetamine;
Lithium; TCA’s ; Opiods, antipsychotics, antibiotics

17. Serotonin Syndrome cont…
P/W:
- Neuromuscular hyperactivity
(tremor, clonus, hyperreflexia)
- Altered mental state (agitation,
excitement)
- Autonomic hyperactivity (fever,
sweating, tachycardia, tachypnoea,
diarrhoea)
Rx: remove the precipitating drugs,
supportive care, the control of agitation
(benzodiazepine), the control of autonomic
instability and the control of hyperthermia

18. Summary

20. Anxiolytics and Hypnotics
-Anxiety conditions: GAD, PTSD, panic disorder, phobias
-Anxiolytics: Used to therapeutically treat anxiety or agitation
-Sedative-hypnotics: Drugs used to sedate or aid in sleep

21. Benzodiazepines
-Most widely used anxiolytic
-Safer and more effective than barbituates
-MOA:
• Binds to GABA receptors (main inhibitory neurotransmitters
of CNS)
• Increase the frequency of chloride channel opening
produced by GABA
• The chloride influx causes hyperpolarization, inhibiting
action potentials

22. Benzodiazepines
Actions:
-Reduces anxiety at low doses
- Sedative & Hypnotic at higher doses
- Anticonvulsant
- Muscle relaxant
- Anterograde amnesia

23. Benzodiazepines
-Can cause psychological and physical dependence if given over a prolonged time
-High addiction potential
-Tolerance and dependence occur
-Should be used for continued severe anxiety or for short periods of time
-Taper on discontinuation
-S/E: drowsiness, confusion, ataxia, cognitive impairment

24. Benzodiazepines

25. Benzodiazepines
Lorazepam: e.g. Ativan
-Anxiety disorders: Initial 2-3mg, 8-12 hrly PRN, not to exceed 10mg/day; Maintenance 2 -
6mg/day divided 8-12 hrly
-Sedation: 0,05mg/kg IM for 1 dose (max 4mg)
Diazepam: e.g. Valium
-Anxiety: 2-10mg PO/IV/IM 6-12 hrly (max 30mg/8hrs)
-Alcohol withdrawal: 10mg PO 6-8hrly in first 24 hrs, then reduce to 5mg PO 6 -8hrly PRN
Clonazepam: e.g. Rivotril
-0,25mg PO 12hrly initially, then increase to 1mg/day after 3 days (max 4mg/day)

26. Other anxiolytic agents:
-5-HT 1A receptor agonists: Buspirone, Ipsapirone
Buspirone:
-Useful for chronic Rx of GAD
-Acts through dopamine & serotonin receptors
-More selective for anxiety(chronic, not acute)
-Less sedation and S/E than benzo
-No anticonvulsant or ms relaxant activity
-No dependence
-S/E: Nausea, dizziness, headache, loss of coordination

27. Other anxiolytic agents:
Barbituates:
-phenobarbital, Thiopental, Pentobarbital
-Non-selective CNS depressant
-Enhances the actions of GABA but has less specific action
-S/E: tolerance, dependence, respiratory and cardiovascular
depression, severe withdrawal symptoms,