1. Management of Depression

2. Mood Disorders
Definition:
Disorders characterized by mood disturbance
( the presence of mood episodes ).
Mood episode :are distinct periods of time in which some abnormal mood is present like depression, mania , mixed- state , or hypomania

3. Major depressive disorder (MDD) Bipolar disorders (BD)
Mood disorders : defined by their patterns of mood episodes .
Major depressive disorder (MDD)
Bipolar disorders (BD)
Dysthymic disorder (DD)
Cyclothymic disorder (CD)

4. What causes depression???
Bio-Psycho-Social Etiology

5. 1) Biology Abnormalities in neurotransmission involving:
norepinephrine
Serotonin
Dopamine
possibly Acetylcholine.
Genetics\familial: 1st degree relative are at much higher risk.

6. 2) Psychology Significant losses Traumas Abuse
neglect during development.
Loss of a parent before the age 11 is life event most associated with development of depression.

7. 3) social
recent stressful events = powerful predictor of depression.

8. Major criteria Major Depressive Episode Depressed mood
Diminished interest or pleasure
Minor criteria
Significant weight loss or gain
Insomnia or hypersomnia
Psychomotor agitation or retardation
Fatigue or loss of energy
Feelings of worthlessness
Diminished ability to think or concentrate; indecisiveness
Recurrent thoughts of death, suicidal attempt or plan
Major Depressive Episode
during the same 2-week period, must include at least 1 Major + 4 Minor:

9. Treatment of depressive disorder
at risk of: suicide , homicide ,unable to care for self
Hospitalization
A)anti-depressant
B)adjuvant medication
Pharmacotherapy
behavioral ,cognitive and family therapy , supportive and dynamic psychotherapy
Psychotherapy
Electroconvulsive therapy (ECT)

10. A) antidepressant medications
SSRI (Selective Serotonin Reuptake Inhibitors)
TCA (Tricyclic Anti Depressant)
MAOI (Monoamine Oxidase Inhibitors)
Atypical Anti Depressant

11. SSRI The most commonly prescribed anti-depressant due to:
Low incidence of side effects.
No food restrictions.
Much safer in overdose.
Mechanism of action : inhibits the presynaptic serotonin pumps increasing serotonin availability in the synaptic clefts.
Examples:
Fluoxetine
Fluvoxamine
Sertraline
Paroxetine
citalopram
Escitalopram

12. Paroxetine (most serotonin specific)
Fluoxetine
longest T1/2 with active metabolites; therefore no need to taper.
Safe in pregnancy, approved for use in children.
Paroxetine (most serotonin specific)
Highly protein bound  several drug interactions
Short T1/2 leading to withdrawal phenomena if not taken consistently
Citalopram
Fewest drug interactions

13. SSRI Side effects: Sexual dysfunction GI disturbance Insomnia Headache
SSRI have significantly fewer side effects than TCA & MAOI due to serotonin selectivity ( they don’t act on histamine, adrenergic, or muscarinic receptors).
Side effects:
Sexual dysfunction
GI disturbance
Insomnia
Headache
Anorexia, weight loss
Akathesia
Seizures
Serotonin syndrome when used with MAOI

14. Serotonin syndrome
caused by taking 2 drugs, both of which increase serotonin  too much serotonin in the brain; like when used with MAOI
symptoms: nausea, diarrhea, palpitations, chills, rigor, restlessness, confusion and lethargy, Hyperreflexia
SSRIs should not be used at least 2 weeks before or after the use of an MAOI .

15. Serotonin Syndrome Treatment:
stop the drug
ABC
Gastric lavage if overdose
IV fluid and NaHCO3
Benzodiazepines (calm the pt, muscle relaxant and prevent seizure)
B-blocker
Mirtazapine
ECT

16. SSRIs increase suicidal thinking and behavior, this is most documented in children and adolescents but may be accurate for adults as well.

17. 2.TCA Inhibit reuptake of norepinephrine & serotonin in the synapses .
Rarely used as first line due to
Higher incidence of side effects
Require more monitoring of dosing
Can be lethal in overdose
Usually started on low dose, then increase to the therapeutic dose (that to avoid the anti-cholinergic side effects).

18. 2.TCA Imipramine Amitriptyline Trimipramine Nortriptyline Desipramine
Examples
Imipramine
Amitriptyline
Trimipramine
Nortriptyline
Desipramine
Clomipramine
Doxepin

19. 2.TCA Side Effects Anti-histamine properties ( sedation)
Anti-adrenergic properties ( arrhythmias, tachycardia, orthostatic-hypotension)
Antimuscarinic effects ( dry mouth, constipation, urinary retention, blurred vision)
Weight gain
Major complications 3Cs ( Convulsion, Coma, Cardiotoxicity).

21. TCAs MOST LEATHAL IN OVERDOSE
TCAs prescribed for bed wetting in children so you should be careful while prescribing the dose

22. 3.MAOI
Increase the availability of biogenic amines ( serotonin, norepinephrine, tyramine, dopamine ) at synapses by irreversible inhibition of oxidase enzymes (MAOI-A, MAOA-B).
Not used as first line due to side effects.

23. 3.MAOI
Examples:
Phenelzine
Tranylcypromine
Isocarboxazid

25. 3.MAOI
Side Effects
Common side effects ( orthostatic-hypotension, drowsiness, weight gain, sex-dysfunction, dry mouth, sleep-disturbances).
Serotonin syndrome if used with SSRI,
Hypertensive crisis, especially if used with sympathomimetcs or tyramine rich foods (cheese, chicken liver, cured meats).

26. 4. Atypical Anti-depressents
SNRI
serotonin / norepinephrine reuptake inhibitors
Venlafaxine
NDRI
norepinephrine / dopamine reuptake inhibitors
Bupropine
SARI
serotonin antagonist and reuptake inhibitor
Nefazodone
trazodone
NASA
norepinephrine and serotonin antagonists
mirtazapine

27. SNRIs
venlafaxine
it increases serotonin and norepinephrine availability in the synaptic cleft.
Venlafaxine is especially useful in treating refractory depression.
S\E: sexual dysfunction, headache, insomnia ,anorexia.
Can increase blood pressure as side effect.

28. NDRIs
Bupropion
binds selectively to the dopamine transporter, but its behavioral effects have often been attributed to its inhibition of norepinephrine reuptake. It also acts as a nicotinic acetylcholine receptor antagonist
NO sexual side effects as in SSRI.
Increase risk of seizures and psychosis at high dose.
Contraindicated in patients with seizure or active eating disorders, and in those currently on MAOI.
Also used in smoking cessation, and seasonal affective disorder.

29. SARIs
Nefazodone
Especially useful in treatment of refractory major depression, major depression with anxiety.
S\E: include nausea, dizziness , orthostatic hypotension, cardiac arrhythmia, sedation and priapism and hepatotoxicity.

30. NASAs mirtazapine Useful in treatment of refractory major depression .
S\E:sedation ,weight gain , dizziness , tremor ,blurred vision .
Rarley  allergic reaction, edema, fainting, seizures, bone marrow suppression, myelodysplasia, and agranulocytosis.

31. B) Adjuvant medications
Stimulants (methylphenidate) still need studies
Antipsychotics useful in patient with psychotic features
Liothyronine(T3), levothyroxine(T4), lithium, l-tryptophan maybe added to convert nonresponding patient to responders

32. psychotherapy Behavioral therapy Cognitive therapy Supportive therapy
Psychoanalysis therapy
Family therapy
Maybe used alone or with pharmacotherapy
Psychotherapy and antidepressant are useful in treating dysthymic

33. Electroconvulsive therapy
Indicated id the patient is unresponsive to pharmacotherapy , or cant tolerate the medications (pregnancy) ,or if we need to decrease symptoms fast (suicide risk )
It’s a safe therapy and we might use it with pharmacotherapy
Before we start the ECT session we give the patient atropine followed by anesthesia and muscle relaxant then a generalized seizure is induced by passing a current of electricity across the brain
The seizure lasts <1 minute

34. Approximately eight treatments are administered over a 2-3 week period
Side effects : retrograde and anterograde amnesia , headache , nausea, muscle soeness

35. Have a pleasant day 