How to Treat Mild and Moderate Depression?

In cases of mild to moderate depression requiring treatment, the question often arises: to what extent are low-intensity measures sufficient, and when is it time to resort to antidepressants? We have compiled recommendations from the national program “Unipolar Depression” regarding therapy choices for you.

For patients with mild to moderate symptoms, the following therapy options are
recommended:
For mild episodes, low-intensity interventions should be offered (such as internet and mobile consultations). If symptoms persist after intervention or if there is a risk of chronicity, psychotherapy may be recommended.

As an alternative, and after careful consideration of the risk-benefit ratio, pharmacotherapy may also be proposed as part of the therapeutic plan.

For moderate severity depressive episodes, patients should be offered psychotherapy and/or pharmacotherapy. Additional internet and mobile consultations may also be appropriate.

Which Antidepressant to Use for Initial Therapy?
If pharmacotherapy is indicated for mild to moderate depressions as part of the therapeutic plan, according to program recommendations, various antidepressants are available from SSRIs to SSRNIs to the herbal substance – St. John’s Wort (Hypericum perforatum). But how to find the suitable antidepressant for your patient?

Since there are minimal differences in efficacy between individual antidepressants, the therapy decision should be made in accordance with the recommendations of the “Unipolar Depression” program, primarily considering: substance safety and interaction profile, patient preferences, and physician prescribing experience.

For mild and moderate depressions, the program recommends, among other options, initiating therapy with St. John’s Wort preparations. However, according to the guidelines, only St. John’s Wort preparations registered as medicinal products for this indication (e.g., Laif®900) should be used for moderate depressions.

For acute severe depressive episodes, a combination of antidepressant and psychotherapy should be offered according to recommendations. Benzodiazepines and Z-drugs (e.g., for severe sleep disturbances or significant agitation) may also be additionally indicated for severe depressive episodes. Regardless of depression severity, supportive measures including physical and light therapy, ergo- and sociotherapy may be offered. St. John’s Wort: Equally Effective as Synthetic Antidepressants In a clinical study comparing high-dose St. John’s Wort extract STW3-VI (Laif®900, 900 mg, once daily) for moderate depressions (F32.1 and F 33.1) over 6 weeks, it demonstrated comparable effectiveness to the SSRI leader citalopram (20 mg/once daily). The non-inferiority test of Laif®900 compared to citalopram was significant (p < 0.0001). Moreover, St. John’s Wort showed significantly better tolerability compared to citalopram.

A prospective open-label study on medical care for moderate depressions confirmed the therapeutically equivalent effectiveness of high-dose St. John’s Wort (Laif®900) and citalopram in everyday practice with significantly better tolerability and compliance compared to SSRIs.

What to Do If Initial Antidepressant Treatment Fails?
For patients in whom antidepressant monotherapy is ineffective within 4 weeks, possible reasons for the lack of response should be assessed:

• Low or subtherapeutic blood levels (monitoring blood levels, genetic predisposition: poor metabolizer or ultra-rapid metabolizer). Dosage adjustment is necessary.
• Presence of somatic and psychiatric comorbidities or depressive comedication? Discontinuation and replacement of interacting substances may be necessary, and attention should also be paid to diet or dietary supplements such as grapefruit or ginkgo.
• Poor patient adherence. Therapeutic adherence should be actively supported.
• Incorrect diagnosis. Change therapy strategy. Note: In elderly patients, reasons for lack of efficacy should be evaluated after 6 weeks due to delayed onset or response. If potential reasons for lack of response have been excluded and it persists, the following steps can be taken with patients receiving antidepressant monotherapy in accordance with clinical guidelines:
• Offer psychotherapy as an adjunct to therapy.
• Augmentation of antidepressant with antipsychotics such as quetiapine or lithium can be considered.
• Consider combination with another antidepressant: SSRI, SNRI, or TCA in combination with mianserin, mirtazapine, or trazodone.
• Switch to an antidepressant with a different mechanism of action no more than once during a depressive episode. Note: Mood stabilizers, dopamine agonists, or psychostimulants should not be used for augmentation.

What to Consider When Switching to Another Antidepressant?
Clinical guidelines provide the option of a one-time switch to an antidepressant with a different mechanism of action. Due to potential interactions, the new antidepressant should be introduced gradually, as should the gradual tapering of the old antidepressant.

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