Goal of Treatment:
• The resolution of current symptoms (i.e., achieving remission)
• The prevention of further episodes of depression (i.e., relapse or recurrence).
Nondrug Therapies for Depression
1-Psychotherapy ( treatment of mild to moderate depression)
• Cognitive-behavioral therapy (CBT);
• behavioral activation (BA);
• interpersonal therapy (IPT)
2- Somatic Interventions
• ECT is recommended for patients with( treatment -resistant depression, severe vegetative
depression, psychotic depression, and severe depression in pregnancy) ,medications may
raise seizure thresholds (benzodiazepines) or promote cognitive impairment (lithium) and
should be discontinued before the procedure.
• Repetitive transcranial magnetic stimulation (rTMS)
• Vagus nerve stimulation—treatment-resistant depression
• Light therapy or phototherapy—is particularly effective for relieving the irritability and
malaise associated with seasonal affective disorder (a milder form of depression ).
3-Lifestyle Adjustments
• Alcohol, recreational drug use, & excessive caffeine consumption should be minimized .
• Increased physical activity & sustained cardiovascular exertion can impart a variety of
health benefits.
• Exercise can regulate appetite, improve sleep patterns, increase energy, enhance self-esteem,
& promote a return to euthymic status.
Factors to Consider in Selecting an Antidepressant :
• History of prior response (personal or family member)
• Safety in overdose
• Adverse effect profiles
• Patient age
• Concurrent medical/psychiatric conditions
• Concurrent medications (e.g., potential for drug interactions)
• Convenience (e.g., minimal titration, once-daily dosing)
• Cost , Patient preference
Decision to prescribe maintenance treatment is based on the following:
• No and severity of previous episodes ; family history of depression ; patient age; Response to
antidepressant; Persistence of environmental stressors.
• Indefinite maintenance treatment is recommended if any one of the following is met:
1. Three or more previous episodes 2. Two or more previous episodes and age older than 50
years 3. One or more and age older than 60 years
Antidepressants
Antidepressants in Pregnancy and Lactation :
1- SSRIs & newer antidepressants:little risk for development fetal malformations ( Class C).
2- paroxetine,(Class D) increased risk for congenital heart defects in newborns.
3- bupropion ,(Class C) risk of congenital abnormalities in animal trials.
4- MAOIs, should be avoided due to increased risks for hypertensive crises.
5- doxepin & fluoxetine associated with the highest concentrations in infants, and it has
been recommended that these medications be avoided.
6- Recent studies with SSRIs suggest that the concentrations achieved in breast milk are lowest
with sertraline, and that paroxetine, citalopram, escitalopram, bupropion and venlafaxine
are somewhere between the extremes of fluoxetine and sertraline.
7- Data are little with mirtazapine, venlafaxine, or duloxetine, but no obvious adverse effects
have been identified among infants exposed to these antidepressants in utero.
8- Similarly, fetal malformations have been rarely reported with TCAs and they are generally
regarded as safe in pregnant women.
Treatment of depression in elderly :
1- The anticholinergic effects of TCA & paroxetine may preclude their use in elderly patients
suffering from narrow angle glaucoma, chronic constipation, or urinary hesitancy.
2- SSRIs are recommended as first line ,but among this list paroxetine is considered the worst
option due to its anticholinergic effects.
3- Mirtazapine (7.5 mg at bedtime ) a judicious choice for elderly depressive patients who
their appetite & sleep have diminished considerably during the past several months.
Antidepressants and cardiac disease :
1- The impact of TCAs on cardiovascular function is a serious concern.The most potentially
dangerous adverse effect of the TCAs is their quinidine like properties.
2- SSRIs appear to be relatively safe in patients with a history of arrhythmias or recent MI.
3- SNRIs do not appear to be arrhythmogenic, but increases in BP may be seen with higher
dosages of venlafaxine in particular (> 150 mg daily).
4- Bupropion and mirtazapine appear unlikely to affect cardiac rhythm or induce arrhythmias
in susceptible patients, Bupropion, however, should be used with caution in patients with
preexisting hypertension because of potential increases in BP.
Antidepressants and diabetes :
1- weight gain appears highest with mirtazapine, TCAs, and MAOIs, and should be avoided.
2- SNRIs (venlafaxine) effective for the diabetic neuropathic pain, but the potential to
increase BP or heart rate should be considered.
3- Sertraline , citalopram, or escitalopram that are unlikely to induce weight gain or
potentiate drug interactions may be a prudent choice in depression with diabetes.
Antidepressants and epilepsy :
1-amoxapine with the highest risk of seizures in overdose, maprotiline &TCAs (collectively).
2-Bupropion is contraindicated in patients with a pre-existing seizure disorder.
3- Since carbamazepine is metabolized by the CYP3A4 isoenzyme, antidepressants that inhibit
this enzyme, such as fluoxetine or fluvoxamine, should be avoided.
4- Sertraline, citalopram or venlafaxine are less likely to inhibit metabolic pathways.
Antidepressants and AIDS
1- fluoxetine & fluvoxamine are best avoided.
2- Inhibition of bupropion metabolism with concurrent adminstration of ritonavir, efavirenz
& nelfinavir may complicate its use in certain circumstances.
3- For appetite stimulation mirtazapine is a reasonable option in some AIDS patients .
4- ECT is safe and affective in the depressed AIDS patient.
Antidepressants and chronic pain
1- TCAs and SNRIs to be quite effective for the neuropathic pain conditions, in addition to
their benefits on anxiety and depression.
2- Concomitant use SNRIs & tramadol should be discouraged due to reports of serotonin
syndrome.
3- TCAs are quite effective for certain pain conditions (weight gain is a concern).
4- Venlafaxine, levomilnacipran, duloxetine is good choice for treatment depression, anxiety.
Depression with Atypical Depression
1- MAOIs (phenelzine, tranylcypromine ,moclobemide) the most effective pharmacologic
agents prescribed for patients with atypical depression, usually after failure of an SSRI.
• MAOI transdermal patch (selegiline) 6 mg patch was approved for atypical depression
by the FDA as safe without the need for dietary restrictions.
Psychotic Depression
1- Aripiprazole, brexpiprazole, quetiapine have also received FDA approval as adjunctive
agents with SSRIs or SNRIs for depression that has poorly responded to monotherapy.
Treatment-Resistant Depression
1-venlafaxine is at least as effective as other antidepressants in these populations, and it has
emerged as a valuable alternative agent.
Venlafaxine is not a potent inhibitor of cytochrome P-450 isoenzymes, so drug interactions are
less of a concern than with certain SSRIs, but duloxetine is a moderate inhibitor of the
CYP2D6 isoenzyme.
The choice venlafaxine is prudent in treatment resistant depression & fairly safe in overdose,
and is generally less activating than fluoxetine.
2- Desvenlafaxine is not affected by CYP2D6 inhibitors; however, CYP3A4 inhibitors may
reduce clearance of the drug.
3- All SNRIs have been associated with serotonin syndrome, so clinicians should be aware of
the potentially dangerous drug combinations.
5- If venlafaxine therapy fails, bupropion is an alternative and at therapeutic dosages, it has
limited adverse effects such as occasional nausea and insomnia or jitteriness.
Bupropion may decrease appetite. The recommended starting dose is 100 mg twice a day
increasing to 100 mg three times a day after at least 3 days.
• Individual doses must not exceed 150 mg and should be given at least 6 hours apart.
Mirtazapine is another alternative for moderate to severe depression (more effective than
fluoxetine)
• Its common adverse effects are sedation and weight gain. • The recommended starting dosage
is 15 mg at bedtime, and the therapeutic dosage ranges from 15 to 45 mg/day.