Treatment of depression considers the severity of disease, patient preferences, treatment availability, and possible adverse difficulties, such as fatigue, insomnia, and current life stresses.
Antidepressants are the second most commonly prescribed drug class
At least 30 drugs are approved by the FDA to treat depression.
Systematic reviews and meta-analysis of 22 anti-depression trials concluded they are more effective than placebo in adults with major depressive disorder, but the effects were mostly modest and tempered by an array of side effects.
Targets synapses that regulate concentrations of serotonin and norepinephrine at postsynaptic monoamine receptors.
Antidepressants are among the most widely prescribed medications with more than 10% of participants in population studies, and the percentage is higher in women and older participants (Mojtabai R).
Cognitive function does not differ between antidepressant users and non users at baseline.
Depression is associated with cognitive impairment and dementia and antidepressant usage does not modify the cognitive change over six years of therapy (Saczynski J S et al).
Reduced levels of allopregnanolone in the CSF normalizes after successful treatment of depression with antidepressants.
In the above study anti-depressing news was not associated with changes in the cognitive function over a six-year period, adjusting for depressive symptoms, comorbidities, and anti-cholinergic load.
In children and adolescents with major depression, obsessive compulsive or other disorders have an average risk of suicidal thinking or behavior of 4% compared to 2% for placebo.
Meta-analysis of antidepressant trials in children randomized to receive antidepressants had twice the rate of suicidal ideation and behavior compared with children who received placebo (Hammad TA et al).
There is evidence that antidepressant drugs protect against or reverse hippocampal atrophy.
That analyses of adult placebo-controlled trials revealed participants 18-24 years of age receiving antidepressants were at an elevated risk of suicidal thoughts and behaviors, while those 25-64 years of age were at equal risk, and those 65 years or older were at lower risk (Stone M et al).
Children and young adults initiating antidepressant therapy at high therapeutic doses are at increased risk of deliberate self harm compared to those with lower doses (Miller M et al).
High risk of depressive relapse after discontinuation of antidepressant therapy.
Patients who feel well enough to discontinue antidepressant therapy compared to those who continue their anti-depressant therapy have a higher risk of relapse of depression by 52 weeks.
Can cause hyponatremia, especially in elderly.
For the most part no increased risk of major congenital malformations associated with first trimester exposure to antidepressants, although a Swedish report of 1.5-2.0 fold increases in cardiovascular malformations to first trimester exposure to selective serotonin reuptake inhibitor paroxetine.
Women’s Health Initiative (WHI) study indicated that antidepressant therapy maybe detrimental with respect to stroke and total mortality in a large cohort of postmenopausal women.
Tricyclic antidepressants (TCA) are effective but not well tolerated, especially in the elderly.
TCAs associated with anti-cholinergic symptoms including dry mouth, constipation, dizziness, sweating, orthostatic hypotension, and blurred vision.
TCAs should be used with caution in the presence of heart disease because of the risk of cardiac complications.
First-generation TCAs include: amitriptyline with a starting dose of 10-25 mg per day and the therapeutic dose of 50 to 200 mg per day.
Doxepin with a starting dose of 10-25 mg a day and therapeutic dosage and 50-200 mg per day.
Imipramine starting dose 10 to 25 mg day and therapeutic dosage 50 to 200 mg a day.
Desipramine starting dose 10-25 mg per day and therapeutic dose 50-200 mg a day.
Nortriptyline starting dose 10-25 mg a day and therapeutic dose 50-150 mg a day
Monoamine oxidase inhibitors (MAOIs) require dietary restrictions.
MAOIs should not be used in combination with SSRIs or any other drug that can increase serotonin activity because of the risk of serotonin syndrome.
MAOI phenelzine starting dose 45 mg day and therapeutic dose 60-90 mg a day.
MAOI tranylcypromine 30 mg daily starting dose and 30-60 mg a day therapeutic dose.
Second generation antidepressants include: selective serotonin reuptake inhibitors (SSRIs).
There are no particular efficacy reasons to favor one SSri over another for the treatment of depression.
Citalopram (Celexa) 10 mg per day starting dose and therapeutic dose 10-60 mg a day.
Citalopram recommendations is not to use doses higher than 40 mg a day because of potential QTc prolongation.
Escitalopram (Lexapro) 5-10 mg a day starting dose and 10-20 mg day therapeutic dose.
Citalopram and Escitalopram are metabolized primarily in the liver by the cytochrome P450 CYP 2C19 enzyme.
Medications that inhibit the CYP2C19 pathway have the potential to cause an increase in serum levels of escitalopram and citalopram.
PPIs Inhibit CYP 2C19 and concomitant use can increase the toxicity of escitalopram man and citalopram.
Fluoxetine (Prozac) 10 mg a day starting dose and 20-60 mg a day therapeutic dose.
Paroxetine (Paxil) 10 mg a day starting dose and 20-50 mg a day therapeutic dose.
Sertraline (Zoloft) 25 mg a day starting dose and 25-200 mg a day therapeutic dose.
Serotonin and norepinephrine reuptake inhibitors (SNRIs):
Venlafaxine (Effexor) starting dose is 37.5 mg daily and therapeutic dose 37.5-375 mg daily.
Duloxetine (Cymbalta) starting dose 20-30 mg a day and therapeutic dose 30-90 mg per day.
Nefazodone (Serzone) 100 mg per day starting dose, and 300-600 mg per day therapeutic dose.
Norepinephrine and dopamine reuptake inhibitors (NDRIs):
Bupropion SR (Wellbutrin) hundred milligrams per day starting dose, and 100-400 mg a day therapeutic dose
Serotonin antagonist(SA):
Mirtazapine (Remeron) 7.5 mg daily starting dose and 15-45 mg therapeutic dose.
SSRI use associated with increased risk of stroke and all cause mortality.
TCA use associated with increased risk of all cause mortality.
Citalopram (Celexa) associated with risk of prolongation of QT interval and can lead to torsade de pointes.
Most common adverse effects of antidepressants are nausea, vomiting, headache, dizziness, constipation, diarrhea, weight gain, sexual dysfunction, and sleep disturbance.
Antidepressants associated with weight gain, and amitriptyline, mirtazapine and paroxetine are associated with the greatest risk.
Other selective serotonin reuptake inhibitors including: citalopram, Escitalopram, fluoxetine, and sertraline have minimal effects on weight.
Serotonin-norepinephrine reuptake inhibitors duloxetine, and venlafaxine have little effect on weight.
Bupropion is the antidepressant with the lowest risk of weight gain, and causes weight loss in many patients.
Trials of psilocybin show short term benefit for depression in selective populations.
Specific types of psychotherapy, including cognitive or cognitive behavioral therapy, behavioral activation, interpersonal therapy, problem-solving therapy, short term psychodynamic psychotherapy, and mindfulness based therapies have demonstrated efficacy in depression.
Meta-analysis show participants with mild depression treated with specific psychotherapies manifest, more efficaciousness than usual care without psychotherapy with small to medium effect.
For mild depression, psychotherapy such as cognitive or cognitive behavioral therapy, behavioral activation, problem-solving therapy, interpersonal therapy, or mindfulness based psychotherapy, have moderate benefit and anti-depressant medication os usually not indicated.
For mild depression, exercise, nutritional supplements, or a digital interventions may be helpful.
For moderate depression either anti-depressant medications or a specific psychotherapies or recommended as first line treatments.
Combined medication psychotherapy may be superior to either treat below for moderately severe or severe depression
Randomized clinical trials comparing the efficacy of first line treatments find no difference between specific psychotherapies and anti-depressant medications. but modestly greater efficacy for combined medication and psychotherapy over either alone, especially for more severe or chronic depression.
Psychotherapy, or combined treatments may yield more durable benefit than anti-depressant medications alone.