Management of Depression

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

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)

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

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

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.

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

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:

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)

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

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

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

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

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 .

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

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

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).

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

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).

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

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.

3.MAOI Examples: Phenelzine Tranylcypromine Isocarboxazid

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).

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

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.

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.

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.

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.

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

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

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

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

Have a pleasant day 