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What are affective disorders?
heterogeneous disorder in which a disturbance of mood is the central feature, although thought and several body functions are affected
types of affective disorders
- major depression
- bipolar affective
symptoms of major depression
- 1. Feelings of sadness, anxiety, guilt, worthlessness, helplessness
- 2. Sleep disturbances, fatigue
- 3. Appetite disturbances (over-eating or anorexia)
- 4. Loss of interest in daily activities
- 5. Difficulties to concentrate
- 6. Suicidal thoughts
causes of depression
- • Reactive/Secondary Depression: after traumatic events
- • Secondary to other diseases
- – substance abuse (alcohol, cocaine, amphetamine)
- – pancreaticcancer
- – Hypothyroidism
- • Endogenous depression: Unknown causes : 75% of cases
- • Genetic component:
- - family history of depression, but less penetration than bipolar disorder
- • Environment: Stress is a major contributing factor
- • Imbalance in monoaminergic neurotransmission – noradrenaline
- – serotonin(5-HT,5-hydroxy-tryptamine)
what is bipolar disorder?
a disorder characterized by extreme changes in mood behavior and energy levels
brain circuitry implicated in reward and depression
monoamine neurotransmitters hypothesis
functional decrease in amine dependent synaptic transmission resulting in depression
classes of neurotransmitters
- amino acids
- biogenic amines
Key to monoamine hypothesis of depression
- 1- Drugs that deplete monoamines are depressant.
- 2- Most antidepressants enhance monoaminergic transmission at
- some point in the synaptic signaling process.
- 3- The concentration of monoamines and their metabolites is reduced in the CSF of depressed patients?? (conflicting results).
- 4- In various post-mortem studies, the most consistent finding is elevation in cortical 5-HT2 binding.
An increased function of the hypothalamic-pituitary-adrenal (HPA) axis or hypothalamic-pituitary-thyroid (HPT) axis in more than 50% of depressed patients.
action of tricyclic antidepressants
- 1. NE reuptake inhibition
- 2. 5-HT reuptake inhibition
- 3. H1 receptor blockade
- 4. H2 receptor blockade
- 5. mACh receptor blockade
- 6. alpha1 receptor blockade
- 7. 5-HT2 receptor blockade
- 8. Na Channel blockade
adverse effects of tricyclic antidepressants
- 1. Antimuscarinic (atropine effect): dry mouth, constipation, urinary retention, aggravation of glaucoma,
- 2. Antihistamine: sedation (tolerance can develop)
- 3. Na channel blockade: QRS, arrhythmias*
- 4. Alphaadrenoceptorsblockade:orthostatic hypotension, tachycardia**
which has less side effects, Tricyclics or SSRIs?
adverse effects of SSRIs
- 1. Anxiety, insomnia, increased appetite, tremors
- 2. GI symptoms
- 3. Sexual dysfunction
- 4. Headache
- 5. Rashes
what is SSRI contraindicated with?
Contraindicated with MAOIs
what is serotonin syndrome?
Caused by combination of drugs that eventually produce increase in brain serotonin levels
what is the symptom of serotonin syndrome?
- • Autonomic: fever, chills, diarrhea
- • Cognition & behavior: agitation, hypomania
- • Motor systems: myoclonus, tremor, weakness, ataxia • Resemble:NeurolepticMalignantSyndrome
what is the treatment of serotonin syndrome?
5-HT antagonists (methysergide)
heterocyclic antidepressants do what?(second and third generations)
block 5-HT and NE reuptake and have other actions
what does bupropion do?
decrease 5-HT, NE & DA reuptake, potent non- competitive antagonist at CNS nicotinic acetylcholine receptors with alpha3beta4 subunit composition
what does nefazodone do?
blocks mACh, decrease 5-HT & NE reuptake; blocks alpha1, 5-HT2A & 5-HT2C receptors
what does venlafaxine do?
decrease 5-HT, NE reuptake
what is second line drug for depression?
what is 1st line for atypical depression?
Adverse effects of MAOI
- – Headache
- – CNS stimulation
- – Dry mouth
- – Weight gain
- – Postural hypotension
- – Antimuscarinic effects
what are the pharmacokinetics of MAOI
- – Clinical effect persists after drug discontinued and absent from
- – Pharmacokinetics parameters no good for predicting doses
- – Must assume effects last for 7 days (Tranylcypromine) to 2-3 weeks (Phenelzine) after discontinuing drug
how long does it take for antidepressants to work?