During the process of preparing these guidelines, multiple gaps in knowledge were detected, for which well-designed studies are required. Proposals from other sources^{21, 78, 167} were also taken into account.

Screening

1. ~ Study the cost-effectiveness of screening programmes in risk groups and in the different levels of healthcare.

Suicide

1. ~ Study the possible effects of various pharmacological or psychotherapeutic treatments on suicidal ideas and behaviours.

Drugs

1. ~ Study the role of drugs in the management of mild depression, at the primary care level.
2. ~ Do comparative studies with multiple arms that compare a drug versus a drug and placebo, with a long term follow-up and a sufficient statistical strength to detect relevant clinical differences.
3. ~ Foster the research of independent studies avoiding the sponsorship of the pharmaceutical industry.
4. ~ Promote studies on the onset of clinical improvement and the time necessary for reaching the maximum level of improvement using different pharmacological treatments.
5. ~ Study the optimum duration of pharmacological treatment in each risk group, drug and dose.
6. ~ Compare the adverse effects of different drugs through larger and more rigorous observational studies.

Relapses

1. ~ Study the characteristics of patients at a high risk of relapse.
2. ~ Perform studies to more accurately determine the time of duration for treatment in patients with a different risk of recurrence.

Resistant depression

1. ~ Study the most effective therapeutic strategies for resistant depression, both pharmacological and non-pharmacological.
2. ~ Comparative studies would be necessary regarding the different possible options to be adopted after a first treatment failure: dose maintenance, antidepressant switch, combination of the same or augmentation with other drugs. It would be important to differentiate between a partial response and the absence of a response, given that it seems that the right treatment strategy could be different.
3. ~ Studies of suitable duration that cover antidepressant and augmentation combination strategies are needed. Studies that evaluate the optimum doses of T3, lithium and pindolol are also necessary.
4. ~ It would also be necessary to design research that assesses the possibility of combining pharmacological treatment with psychotherapeutic treatment in the management of resistant depression.

Psychotherapy

1. ~ Use medium- and long-term clinical trials to study the efficacy of the various types of psychotherapy in the different levels of healthcare.
2. ~ Trials for determining the most appropriate duration of psychotherapeutic treatment.
3. ~ Design research that assesses the possibility of combining pharmacological treatment with psychotherapeutic treatment.

ECT

1. ~ Promote additional research to evaluate the long-term effect of the technique and the efficacy of maintenance ECT as treatment for depression.

Self-help

1. ~ Develop adapted material for self-help programmes and test its efficacy through controlled studies.

Support groups

1. ~ Determine the role of social support for isolated or vulnerable people.

Exercise

1. ~ New clinical trials are needed, which, while differentiating the sub-groups of mild, moderate and severe depression, compare the effects of different forms of physical exercise and clarify the dose and appropriate intensity of the same.

Acupuncture

1. ~ Perform additional, randomised controlled trials, with adequate statistical power and a good methodological design, which correctly evaluate the efficacy of acupuncture, thereby comparing this technique with other therapeutic alternatives and evaluating the long-term outcomes and side effects.

Generales

1. ~ Study the effect of implementing corrective measures in the system, which will allow detecting quality problems and monitoring the evolution of those problems.
2. ~ Study the effect of integrating help tools for the management of depression in electronic medical histories.
3. ~ Study appointment improvement systems and their effect on therapeutic compliance.
4. ~ Study the effectiveness of the various methods of implementing clinical practice guidelines.