This document discusses drugs used to treat affective disorders such as depression and mania. It describes the mechanisms and side effects of tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and lithium. TCAs have anticholinergic side effects. Chlomipramine is used for obsessive compulsive disorder. Imipramine causes sedation. MAOIs carry risk of hypertensive crisis. Seizure is a side effect of bupropion.

1. Drugs Used in Affective
Disorders

2. MOOD/MOOD DISORDER
• Sustained emotion

3. INCIDENCE
• Higher in women than in men
• Between ages 25 to 44

4. Etiology of Depression
Biogenic Amine Hypothesis
• Depression and mania are due to an alteration in neuronal
and synaptic catecholamine concentration at adrenergic
receptor sites in the brain.
– Depression: deficiency of catecholamine,
especially norepinephrine
– Mania: excess amines

5. ETIOLOGY
• Biogenic amine theory
• Dysregulation theory
• Family history

6. Range of emotions
• Euthymia
• Hypomania
• Euphoria
• Mania
• Dysthymia
• Dysphoria
• Depression

7. Clinical features of major depression
One of the following must be present:
– Depressed mood
– Anhedonia (i.e., loss of interest or pleasure)
Plus four or more of the following:
– Decreased or increased appetite
– Unintentional weight loss or gain
– Insomnia or hypersomnia
– Psychomotor agitation or retardation
– Fatigue or loss of energy
– Feelings of worthlessness or excessive or inappropriate
guilt
– Diminished ability to think or concentrate or
indecisiveness
– Recurrent thoughts of death and/or suicidal ideation
– Suicide attempt

8. Treatment
• Psychotherapy
• Pharmacotherapy
• ECT

9. Treatment phases for depression
Treatment phase Duration Goal
Acute 6 weeks Resolve
symptoms
Continuation 6-9 months Prevent relapse
Maintenance 3-5 years of
lifelong
Prevent
recurrence in high
risk patients

10. Drug selection/administration
• All drugs are equally effective
• Half the lowest dose
• 1-2 wks
• 4-6wks
• Try onother class

11. Changing antidepressant
• 2 wks
• 5 wks with fluoxetine

12. Clinical manifestations of serotonin syndrome and serotonin
withdrawal syndrome
Classification of
dysfunction
Serotonin syndrome Serotonin
withdrawal
syndrome
Cognitive-
behavorial
dysfunction
Confusion
Hypomania
Agitation
none
Autonomic
nervous system
dysfunction
Diarrhea Diaphoresis
Shivering
Fever
Changes in blood
pressure
Nausea and vomitting
Flu-like symptoms
Dizziness
Light headedness
Chills
Sleep
disturbances
Neuromuscular
dysfunction
Myoclonus
Hyperreflexia
Tremor Seizure
Death
Lethargy
Myalgia sensory
disturbances (e.g.,
paresthesia)

13. Selective 5-HT uptake inhibitors (SSRI)
• 1st
line for depression
• Actions similar in efficacy & time course to TCA
• Acute toxicity is less than that of MAOI or TCA
• Side-effects include nausea, insomnia & sexual
dysfunction.
• dangerous 'serotonin reaction'
– (hyperthermia, muscle rigidity, cardiovascular collapse)
can occur if given with MAOI.
• Long half-lives

14. SSRI
• Fluoxetine
• Fluvoxamine
• Nefazodone
• Paroxetine
• Sertraline
• Trazodone
• venlafaxine

15. SSRIs
• Am bec of its stimulatory effect
• Metabolize via cytochrome P450

16. SSRI’s
• Fluoxetine- bulimia
– Most stimulatory
– For depression with negative symptoms
• Paroxetine
– Most sedating
– Depression with anxiety and insomnia
• Sertraline
– Less stimulatory and less sedating

17. Tricyclic antidepressants (TCA)
• TCA are chemically related to phenothiazine
• 2nd
line of choice
• Inhibit reuptake of serotonin and norepinephrine
• Important side-effects:
– sedation (H1-block), postural hypotension (α-adrenoceptor block),
dry mouth, blurred vision, constipation (muscarinic block),
occasionally mania and convulsions.
– Risk of ventricular dysrhythmias through potassium channel block.

18. Cyclic Antidepressants
• Tricyclic antidepressants—primary: amitriptyline
(Elavil), doxepin (Sinequan), imipramine (Tofranil)
• Tricyclic antidepressants—secondary:
desipramine (Norpramin), nortriptyline (Aventyl),
protriptyline (Vivactil)
• Tetracyclic antidepressants:
amoxapine (Asendin), maprotiline (Ludiomil)

19. Cyclic Antidepressants
Mechanism of Action
• Block reuptake of neurotransmitters, causing
accumulation at the nerve endings.
• It is thought that increasing concentrations of
neurotransmitters will correct the abnormally
low levels that lead to depression.

20. Cyclic Antidepressants
Mechanism of Action—Drug Effects
Blockade of norepinephrine:
– antidepressant, tremors, tachycardia, additive
pressor effects with sympathomimetic drugs
Blockade of serotonin:
– antidepressant, nausea, headache, anxiety,
sexual dysfunction

21. Cyclic Antidepressants
Therapeutic Uses
• Depression
• Childhood enuresis (imipramine)
• Obsessive-compulsive disorders
(clomipramine)
• Adjunctive analgesics
• Trigeminal neuralgia

22. TCA
– PM DOSAGE ALL- SEDATING ACTIVITY
– 4-6 WKS- FULL RESPOSE
– 1 WK ASSYMPTOMATIC RELIEF
– ANTICHOLINERGIC SIDE EFFECTS

23. Cyclic Antidepressants
Side Effects
• Sedation
• Impotence
• Orthostatic hypotension
• Older patients:
– dizziness, postural hypotension, constipation,
delayed micturation, edema, muscle tremors

24. TCA
• TCA USER
• HEALTHY
• NONSUICIDAL
• REFRACTORY TO NEWER DRUGS

25. Monoamine oxidase inhibitors
(MAOI)
• Action is long lasting (weeks) due to irreversible inhibition of
MAO A & B.
– Moclobemide has a short duration of action
• 3rd
line of choice
• Main side-effects:
– postural hypotension (sympathetic block)
– atropine-like effects (as with TCA);
– weight gain
– CNS stimulation
– Serotonin syndrome
– liver damage (rare). ISOCARBOXAZID

26. Antidepressants: MAOIs Hypertensive
Crisis and Tyramine
• Ingestion of foods and/or drinks with
the amino acid TYRAMINE leads to
hypertensive crisis, which may lead
to cerebral hemorrhage, stroke,
coma, or death

27. Antidepressants: MAOIs Hypertensive
Crisis and Tyramine
Avoid foods that contain tyramine!
• Aged, mature cheeses (cheddar, blue, Swiss)
• Smoked/pickled or aged meats, fish, poultry (herring,
sausage, corned beef, salami, pepperoni, paté)
• Yeast extracts
• Red wines (Chianti, burgundy, sherry, vermouth)
• Italian broad beans (fava beans)

28. MAOI
• ATYPICAL DEPRESSION
• HYPERSOMNIA
• AGITATION
• ANXIETY

29. Monoamine oxidase inhibitors
(MAOI)
• Phenelezine,Tranylcypromine,
• Isocarboxazid
– Rarely clinical due to serotonin syndrome
– hypertensive crisis- most common (tyramine-rich foods)
– 3 -4 wks- do not discontinue
– Insomnia effect – not at pm

30. Side effects
• Othostatic hypotension
• Weight gain
• Edema
• Sexual dysfunction
• Hepatocellular damage-isocarboxacid

31. MANIA

32. Etiology
• Genetics
• Neurotransmitter level
• GABA level
• Calcium
• G proteins
• Psychosocial and physical stressors

33. Symptoms of mania
• Grandiose ideations or expansive self-esteem
• Decreased need for sleep
• Pressured speech
• Racing thoughts or flight of ideas
• Distractability
• Psychomotor agitation
• Engaging in dangerous, high-risk activities

34. LITHIUM
• Mechanism of Action
–?
–alters intracellular second messengers:
adenyl cyclase-cyclic AMP system and the G
protein-coupled phosphoinositide systems
(NE and serotonin)
–alters ion channel function
–alters metabolism of GABA

35. LITHIUM
• Adverse effects
–Narrow therapeutic index
–Therapeutic range: 0.5-1.5mEq/L
–Minor S/E: tremors, polyuria,
GI distress,
memory problems, acne,
weight gain
–Long-term S/E: hypothyroidism
–Toxic levels: ataxia, tremors, confusion, coma, sinus
arrest, death

36. LITHIUM
Baseline labs Adverse effects
Thyroid
function
hypothyroidism
BUN/Crea Renal
insufficiency
Electrolytes
(esp.sodium)
Dec. Na
CBC leukocytosis

37. • Alternative mood-stabilising drugs
(e.g. carbamazepine, valproate,
gabapentin,clonazepam)

38. Summary
• ANTICHOLINERGIC-TCA
• CHLOMIPRAMINE-OC
• IMIPRAMINE –NOCTURNAL
• MAOI- HYPERTENSIVE CRISIS
• SEIZURE-SE OF BUPROPION