Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
antidepressant monotherapy
Pharmacotherapy is a first-line therapy. Meta-analyses suggest that antidepressant pharmacotherapy may be more effective than psychotherapy for the treatment of patients with persistent depressive disorder.[44][90][91][92] Pharmacotherapy was shown not to be more effective than placebo in individuals with physical illness complicating depression.[93]
The choice of antidepressant is the same for more acute forms of depression, the clinician may be best guided by patient characteristics, starting with the generally safer SSRIs where possible. There is insufficient evidence to recommend one second-generation antidepressant over another.[94][95] Usual adult doses can be used for the treatment of patients with persistent depressive disorder, with gradual dose increments to the higher dose levels as tolerated.[95]
Typically, a selective serotonin-reuptake inhibitor (SSRI) is started, and then if the first medication is not tolerated or effective, it may be beneficial to switch to an antidepressant of another class such as bupropion (sustained- or extended-release)[70] or a serotonin-norepinephrine reuptake inhibitor (SNRI). Subsequent options include combination pharmacotherapy. Combined drug treatment must be done with attention to possible drug-drug interactions (e.g., risk of serotonin syndrome with SSRI plus an MAOI.
The key to treatment is to give doses adequate to treat PDD symptoms, for relatively long periods of time (compared with treatment of acute forms of depression).
There are limited data regarding treating children, but depressed adolescents should be systematically screened, and assessed for suicide risk, and provided appropriate treatment referrals with evidence-based treatment if available.[38][56] The usual caveats considering antidepressants and increase in suicidal thinking in young patients should be followed.[83][84] A review of continuation antidepressant treatment in children and adolescents with major depression or dysthymia showed lower rates of relapse with active medication treatment compared with placebo, though the number and quality of studies is limited.[110] Young patients should be monitored closely for changes in behavior and/or the emergence of suicidal thinking. Family members must be made aware that such changes can occur during treatment, and should contact the prescriber if need be. The only antidepressants approved for use in children with depression in the US are fluoxetine (for children ages 8 years and over) and escitalopram (for children ages 12 years and over).
[ 
]
In pregnant patients, clinicians should carefully discuss the risks of remaining on antidepressant treatment during pregnancy, against the risks of stopping or avoiding antidepressants and exposing the fetus to the harmful effects of depression.
See Depression in adults.
Primary options
sertraline: adults: 50 mg orally once daily initially, increase according to response, maximum 200 mg/day
OR
citalopram: adults: 20 mg orally once daily initially, increase according to response, maximum 40 mg/day
OR
fluoxetine: children 8-17 years of age: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day; adults: 20 mg orally once daily initially, increase according to response, maximum 80 mg/day
OR
escitalopram: children ≥12 years of age and adults: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day; higher doses have been used for this indication, so consult specialist for guidance
OR
bupropion hydrochloride: adults: 150 mg orally (sustained-release or extended-release) once daily initially, increase according to response, maximum 400 mg/day given in 2 divided doses
OR
duloxetine: adults: 30 mg orally once daily initially, increase according to response, maximum 120 mg/day
OR
venlafaxine: adults: 37.5 mg/day orally (sustained-release) once daily, increase according to response, maximum 375 mg/day
OR
desvenlafaxine: adults: 50 mg orally once daily, increase according to response, maximum 100 mg/day
OR
vortioxetine: adults: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day
OR
vilazodone: adults: 10 mg orally once daily initially, increase according to response, maximum 40 mg/day
OR
levomilnacipran: adults: 20 mg orally once daily initially, increase according to response, maximum 120 mg/day
Secondary options
imipramine: adults: 25-75 mg orally once daily at bedtime initially, increase according to response, maximum 300 mg/day
OR
mirtazapine: adults: 15 mg orally once daily initially, increase according to response, maximum 60 mg/day
OR
paroxetine: adults: 10 mg orally (immediate-release) once daily initially, increase according to response, maximum 50 mg/day; 12.5 mg orally (controlled-release) once daily initially, increase according to response, maximum 75 mg/day
supportive interventions
Treatment recommended for SOME patients in selected patient group
Exercise has been studied as a treatment for depression, though not specifically for persistent depressive disorder, and results suggest benefit in some patients comparable to medication.[100]
[ ]
In one study, regular exercise produced frequent sustained remission at 1-year follow-up.[111] Exercise may have beneficial effects on neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in people diagnosed with depression.[102] A small study showed that body psychotherapy in patients with chronic depression, including exercises, movement strategies, and sensory awareness procedures, led to improved depressive symptoms compared with a waiting-list control.[112] Data on lifestyle modification, including adoption of Mediterranean diet and increased exercise, have shown benefit for depressive symptoms and disorders.[104]
One study suggested that yoga might be effective in some patients with depression, although the authors stated that further studies were needed.[105]
Low-quality evidence suggests acupuncture may reduce the severity of depression compared to no treatment, wait list, treatment as usual, or control acupuncture; however, there is no clear evidence regarding the risk of adverse events or comparisons to other treatments like medication or psychotherapy.[106]
[ ]
Internet-based therapies have been shown to be effective for treatment of depression, including some studies including individuals with persistent depressive disorder.[107]
supportive interventions
Treatment recommended for SOME patients in selected patient group
Exercise has been studied as a treatment for depression, though not specifically for persistent depressive disorder, and results suggest benefit in some patients comparable to medication.[100]
[ ]
In one study, regular exercise produced frequent sustained remission at 1-year follow-up.[111] Exercise may have beneficial effects on neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in people diagnosed with depression.[102] A small study showed that body psychotherapy in patients with chronic depression, including exercises, movement strategies, and sensory awareness procedures, led to improved depressive symptoms compared with a waiting-list control.[112] Data on lifestyle modification, including adoption of Mediterranean diet and increased exercise, have shown benefit for depressive symptoms and disorders.[104]
Internet-based therapies have been shown to be effective for treatment of depression, including some studies including individuals with persistent depressive disorder.[107]
One study suggested that yoga might be effective in some patients with depression, although the authors stated that further studies were needed.[105] Low-quality evidence suggests acupuncture may reduce the severity of depression compared to no treatment, wait list, treatment as usual, or control acupuncture; however, there is no clear evidence regarding the risk of adverse events or comparisons to other treatments like medication or psychotherapy.[106]
[ ]
combined pharmacotherapy-psychotherapy
A combination of pharmacotherapy-psychotherapy is an alternative first-line therapy.
Patients with chronic forms of depression require a longer treatment period, more psychotherapy sessions, and/or higher doses of antidepressant medication than do patients with acute forms of depression.[43]
Only one study has demonstrated the effect of combined pharmacotherapy-psychotherapy. This was conducted in patients with chronic major depressive disorder. The study showed that combined psychotherapy (cognitive behavioral analysis system of psychotherapy [CBASP]) and an antidepressant had a better acute (12-week) outcome than psychotherapy or medication monotherapy.[43]
Antidepressant choice is the same as for other forms of depression. Usual adult doses can be used for the treatment of patients with persistent depressive disorder, with gradual dose increments to the higher dose levels as tolerated.
There are limited data regarding treating children, but depressed adolescents should be systematically screened, and assessed for suicide risk, and provided appropriate treatment referrals with evidence-based treatment if available.[38][56] The usual caveats considering antidepressants and increase in suicidal thinking in young patients should be followed.[83][84] A review of continuation antidepressant treatment in children and adolescents with major depression or dysthymia showed lower rates of relapse with active medication treatment compared with placebo, though the number and quality of studies is limited.[110] Young patients should be monitored closely for changes in behavior and/or the emergence of suicidal thinking. Family members must be made aware that such changes can occur during treatment, and should contact the prescriber if need be. The only antidepressants approved for use in children with depression in the US are fluoxetine (for children ages 8 years and over) and escitalopram (for children ages 12 years and over).
[ ]
Cognitive behavioral therapy and interpersonal therapy are both recommended options to consider for children and adolescents with persistent depressive disorder, according to American Academy of Child and Adolescent Psychiatry practice guidelines.[40]
A small study showed that body psychotherapy in patients with chronic depression, including exercises, movement strategies, and sensory awareness procedures, led to improved depressive symptoms compared with a waiting-list control.[103]
In pregnant patients, clinicians should carefully discuss the risks of remaining on antidepressant treatment during pregnancy, against the risks of stopping or avoiding antidepressants and exposing the fetus to the harmful effects of depression.
See Depression in adults.
Primary options
sertraline: adults: 50 mg orally once daily initially, increase according to response, maximum 200 mg/day
or
citalopram: adults: 20 mg orally once daily initially, increase according to response, maximum 40 mg/day
or
fluoxetine: children 8-17 years of age: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day; adults: 20 mg orally once daily initially, increase according to response, maximum 80 mg/day
or
escitalopram: children ≥12 years of age and adults: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day, higher doses have been used for this indication, consult specialist for guidance
or
bupropion hydrochloride: adults: 150 mg orally (sustained-release or extended-release) once daily initially, increase according to response, maximum 400 mg/day given in 2 divided doses
or
duloxetine: adults: 30 mg orally once daily initially, increase according to response, maximum 120 mg/day
or
venlafaxine: adults: 37.5 mg/day orally (sustained-release) once daily initially, increase according to response, maximum 375 mg/day
or
desvenlafaxine: adults: 50 mg orally once daily initially, increase according to response, maximum 100 mg/day
or
vortioxetine: adults: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day
or
vilazodone: adults: 10 mg orally once daily initially, increase according to response, maximum 40 mg/day
or
levomilnacipran: adults: 20 mg orally once daily initially, increase according to response, maximum 120 mg/day
-- AND --
psychotherapy
Secondary options
imipramine: adults: 25-75 mg orally once daily at bedtime initially, increase according to response, maximum 300 mg/day
or
mirtazapine: adults: 15 mg orally once daily initially, increase according to response, maximum 60 mg/day
or
paroxetine: adults: 10 mg orally (immediate-release) once daily initially, increase according to response, maximum 50 mg/day; 12.5 mg orally (controlled-release) once daily initially, increase according to response, maximum 75 mg/day
-- AND --
psychotherapy
supportive interventions
Treatment recommended for SOME patients in selected patient group
Exercise has been studied as a treatment for depression, though not specifically for persistent depressive disorder, and results suggest benefit in some patients comparable to medication.[100]
[ ]
In one study, regular exercise produced frequent sustained remission at 1-year follow-up.[111] Exercise may have beneficial effects on neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in people diagnosed with depression.[102] A small study showed that body psychotherapy in patients with chronic depression, including exercises, movement strategies, and sensory awareness procedures, led to improved depressive symptoms compared with a waiting-list control.[112] Data on lifestyle modification, including adoption of Mediterranean diet and increased exercise, have shown benefit for depressive symptoms and disorders.[104]
Internet-based therapies have been shown to be effective for treatment of depression, including some studies including individuals with persistent depressive disorder.[107]
One study suggested that yoga might be effective in some patients with depression, although the authors stated that further studies were needed.[105] Low-quality evidence suggests acupuncture may reduce the severity of depression compared to no treatment, wait list, treatment as usual, or control acupuncture; however, there is no clear evidence regarding the risk of adverse events or comparisons to other treatments like medication or psychotherapy.[106]
[ ]
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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