Depression: Drug Therapy

Therapy goals

  • Goals of drug therapy for depression are, in addition to mood elevation, activation or, if necessary, attenuation (depending on the exact symptoms).
  • The goal of acute therapy for unipolar depression is to relieve the patient’s suffering, to treat the symptoms of the current depressive episode and to achieve the greatest possible remission (permanent subsidence of symptoms) of the depressive episode, as well as to restore occupational and psychosocial performance.
  • The goal of maintenance therapy by continuing the drug and / or psychotherapeutic treatment to stabilize the still unstable condition of patients to the extent that a relapse can be avoided.
  • Relapse prophylaxis, i.e. to prevent the occurrence of a new episode of the disease in the long term.

Therapy recommendations

  • The S3 guideline/Nationale VersorgungsLeitlinie Unipolare Depression recommends: “In the case of a mild depressive episode, if it can be assumed that the symptoms will subside without active treatment, depression-specific treatment can initially be dispensed with in the sense of active wait-and-see support. If the symptoms persist after a check-up after 14 days at the latest, or if they have worsened, a decision should be made with the patient about the initiation of a specific therapy. “Note: In mild depression, a difference between placebo and antidepressants is not statistically demonstrable, so very few patients are likely to benefit from treatment with antidepressants. Therapy of choice are: Psychotherapy, explaining sleep hygiene rules, lifestyle changes (nicotine restriction (renunciation of tobacco); moderate alcohol consumption to renunciation, sufficient sleep, endurance sports) – see below “Further therapy”.
  • Subsequent recommendations according to S3 guideline/NVL, Unipolar depression, long version, 2015:
    • For the treatment of an acute moderate depressive episode, patients should be offered drug therapy with an antidepressant [recommendation grade A].
    • For acute major depressive episodes, combination treatment with drug therapy and psychotherapy should be offered [recommendation grade A].
    • In dysthymia (persistent affective disorder in which there is chronic mild depressed mood in the affected person) and double depression, the indication for pharmacological treatment should be evaluated.
  • Acute therapy:
  • Other agents: maprotiline, mianserin (tetracyclic antidepressants); moclobemide, tranylcypromine (MAO inhibitors), are used only in treatment-resistant depression because of the side effect profile (reserve therapeutics).
  • Major depression – ketamine (anesthetic; activation of opioid receptors) can relieve major depression over time after a single injection; breaks through major depression within one hour (“hit and go” effect)Note: Depressive relapses occurred 50-70% less frequently under maintenance therapy with esketamine.
  • Notes on antidepressant therapy:
    • With antidepressants, an acute (sedative/calming) and the actual antidepressant effect must be distinguished.
    • Combination therapy should be used only in individual cases. In such cases, augmentation with antipsychotics in low doses should be considered.
    • Review of efficacy: all agents have in common that the effect occurs only after two to four weeks. In contrast, side effects often dominate the initial period.Therapy resistance is when a patient does not respond immediately to a standard therapy procedure. Pseudotherapy resistance is when diagnostics or therapy were inadequate. The results of the Early Medication Change (EMC) study suggest that early drug switching after two weeks is an option. Serum level determination is required for non-response to an antidepressant (therapeutic drug monitoring, TDM). Numerous reasons can cause pseudotherapy resistance: inadequate dosing, patient noncompliance, abnormalities in genetic metabolism, pharmacologically induced depression (see under Causes/Medications), and unrecognized somatic or psychiatric comorbidities (concomitant diseases).
    • For therapy should always be carried out psychotherapy.
  • In case of resistance to therapy:
    • Lithium augmentation (mood stabilizer), i.e., addition of lithium when a patient does not respond to at least one antidepressant monotherapy
    • Antidepressant high-dose therapy (applies only to TZA, tranylcypromine, and venlafaxine).
    • Combination of two antidepressants: combination of a reuptake inhibitor (SSRI, SNRI pder TZA) + blocker of the presynaptic autoreceptor (mianserin, mirtazapine or trazodone).
    • Irreversible monoamine oxidase (MAO) inhibitor: tranylcypromine.
  • Maintenance therapy: once efficacy has been established, transition to maintenance therapy (period: 4-9 months from remission of symptoms): antidepressants should be taken for at least 4-9 months beyond the remission of a depressive episode, because this can significantly reduce the risk of relapse. In this maintenance phase, the same dosage as in the acute phase should be continued [recommendation grade A].
  • Relapse prophylaxis: In patients with a high relapse tendency (propensity to recurrence of the disease), long-term relapse prophylaxis is indicated; medications are already in the acute therapy and maintenance therapy effective antidepressants and dosages in question (at least 2 years for long-term prophylaxis); if necessary, also lithium salts in suicidal patients / suicidal patients [Recommendation grade A].
  • Antidepressant therapy during:pregnancy and lactation (see below).
  • See also under “Other therapy” (sports medicine, psychotherapy; electroconvulsive therapy (ECT; synonym: electroconvulsive therapy), in patients who do not respond to antidepressant therapy).

Caveat. The FDA warns of increased suicidality (suicide risk) from SSRIs in minors after children and adolescents expressed increased suicidal ideation in controlled studies using SSRIs. A twofold increased risk of suicide was demonstrated when treated from the start with a high dose rather than the standard dose. Further references

  • First choice for minors with acute depression (in combination with cognitive behavioral therapy, CBT) is fluoxetine (selective serotonin reuptake inhibitor (SSRI))

Definition of symptom changes

Response (“Response”) Reduction in depressive symptomatology in relevant scales (e.g., BDI, PHQ-D, HDRS) by 50% of baseline at treatment initiation.
Remission Complete recovery to the original functional state or a largely symptom-free state after acute therapy.
Relapse (“Relapse”) Recurrence of a depressive episode during maintenance therapy.
Full recovery Symptom-free period for approximately 6 months after remission.
Recurrence Recurrence of a depressive episode after complete recovery.

Classification of the success of therapy

Symptom reduction <20 = no effect or effect
Symptom reduction 20-50%. = minimal effect or low effect
Symptom reduction > 50% = partial remission
Symptom reduction = 100% = Complete remission*

* A symptom reduction of 100% is to be understood in relation to falling below the cut-off value for depression of the respective test procedure.

Phytotherapeutics

Active ingredients Dosage Special features
St. John’s wort 3 x 300-350 mg/d (dry matter). Cytochrome 3A4 induction!
  • Mechanism of action: inhibits central reuptake of serotonin, norepinephrine, and dopamine and leads to downregulation of central serotonin receptors and noradrenergic beta receptors; has mood-lifting, drive-enhancing, and relaxing effects
  • Latency period 10-14 days
  • Indications: mild depression; also mild or moderate depressive episode, if appropriate.
  • Side effects:
    • Risk of photosensitization with symptoms similar to sunburn. Thus, no exposure to natural or artificial sunbathing!
    • Allergic reactions (exanthema), gastrointestinal complaints; fatigue and restlessness.
  • Caution with combination therapy: CYP 3A4 induction.

Antidepressant psychopharmacotherapy in pregnancy and lactation

Pregnancy

Breastfeeding phase

  • Breastfeeding is generally compatible with taking antidepressants.
  • Serum level checks are not usually necessary in infants.
  • There are no recommendations on the interval between taking the drug and the initiation of breastfeeding.
  • Caveat (Warning): in premature infants, low body weight, or infant illness (decreased metabolic ability).
  • Adverse reactions have occurred in infants taking fluoxetine and venlafaxine.

Other notes

  • Women who have postpartum (“after delivery”) depression often also have premenstrual (“before menstruation“) depression. Typically, these women do well during pregnancy. These women represent a subgroup of hormonal depression that may also be more likely to have menopausal depression. This collective responds well to transdermal hormone therapy

Chronic pain, sleep disturbances, and depression

The symptom cluster “pain, sleep disorders and depression” is very common. This is not surprising, since the three symptom areas are interrelated. On the one hand, they have overlapping areas, and on the other hand, they reinforce each other:

  • Depression is often accompanied by chronic pain.
  • Repeated sleep deprivation can relieve depression, but it also increases pain sensitivity.
  • Disturbed sleep can thus also be the cause of increased pain sensitivity!
  • Chronic pain is associated with a significantly increased prevalence of insomnia or impaired sleep quality; patients with chronic pain often develop depression

For drug therapy for pain, see “Chronic Pain/Drug Therapy.” For drug therapy for sleep disorders, see “Sleep Disorder/Medicinal Therapy.”

Other comorbidities

  • Apoplexy patients should not initially hold antidepressant prophylaxis. If depression occurs, anticholinergic substances should not be used primarily!
  • Tumor patients with mild depression should receive psychotherapy; for moderate to severe depression, an antidepressant, preferably an SSRI.
  • Diabetic patients with mild depression should receive psychotherapy; for moderate to severe depression, preferably an SSRI, as these promote weight loss.

Supplements (dietary supplements; vital substances)

Suitable dietary supplements should contain the following vital substances:

In the presence of insomnia (sleep disorders) as a result of depression, see below Insomnia/Medicinal Therapy/Supplements. Note: The listed vital substances are not a substitute for drug therapy. Supplements are intended to supplement the general diet in the particular life situation.