Depression: Treatment

Algorithms for treating depression

There are several approaches to treating a patient with depression. The following factors should be taken into account: the presence or absence of episodes of major depression in the anamnesis, the severity of the present episode, the degree of patient support from the family and loved ones, comorbid psychic or somatic disorders, the presence of suicidal intentions.

[1], [2], [3], [4], [5], [6], [7]

Beginning of depression treatment

The key to effective treatment is an accurate diagnosis of a major depressive episode with the exclusion of other conditions that can manifest in a similar way, especially bipolar disorder. The initial state is useful to quantify using rating scales. This is the scale of Bek's depression, the scale of Carroll's depression, the scale of self-evaluation of Tsung's depression, which are questionnaires filled by patients, and the clinical rating scales with which the patient himself assesses the patient's condition: the scale of depression of Hamilton, the scale of depression of Montgomery-Asberg. The use of these scales allows quantifying the effectiveness of therapy and helps determine the state of complete euthymy - the ultimate goal of treatment.

Read also: 8 things you need to know about antidepressants

Pharmacotherapy is the main method of treating depression, but it can be combined with psychotherapy. Antidepressants are indicated for severe or mild depression. Currently, there is a wide selection of drugs that are fairly safe and convenient to use. Treatment is recommended starting with new generation drugs, while MAO and TCA inhibitors are left in reserve, in case of inefficiency of first-line drugs.

Before you designate a particular drug, you should make sure of the diagnosis, exclude possible somatic or neurological causes of depression, discuss the diagnosis and treatment options with the patient, his family or people close to him. Each patient with an affective disorder should be examined for suicidal ideation. For this, for example, the patient can be asked: "Does it sometimes happen that your deeds are so bad that you have a desire to commit suicide or damage yourself?" The frequency of repeated examinations of the patient depends on the severity of the depressive episode and the effectiveness of the treatment.

The following factors influence the choice of antidepressant.

1. Anamnestic data on the effectiveness of previous therapy in a patient or his relatives. If any drug or class of drugs was effective, then treatment should begin with them. The decision on maintenance therapy should be made depending on the number and severity of previous episodes.
2. Safety of preparations. Although modern antidepressants are much safer, including in case of an overdose than TCAs and MAO inhibitors, the choice of an antidepressant should take into account the possibility of drug interaction, as well as the presence of co-morbidities that may increase the risk of side effects.
3. Spectrum of side effects. Most of the new generation drugs have the most favorable balance of risk and effectiveness. It is important to inform the patient of possible side effects and available therapeutic options.
4. Compliance. Almost all antidepressants of the new generation are taken no more often than twice a day, and most - once a day. Due to the convenience of use and good tolerability, the compliance with modern antidepressants is significantly higher than with traditional drugs.
5. With the cost of drugs. Although the cost of therapy may seem high (often from $ 60 to $ 90 per month - depending on the dose), but nevertheless it is less than the costs that are unavoidable in the absence of treatment or in the case of low patient compliance with generic TCAs, cheaper, but more often causing side effects.
6. The possibility and necessity of controlling the concentration of the drug in the blood. This applies only to some TCAs of the older generation, since antidepressants of the new generation have a therapeutic concentration of the drug in the plasma to be determined.
7. Mechanism of action. The pharmacological effect of an antidepressant is important to consider when choosing not only the initial drug, but also the subsequent drug, if the first was ineffective.

In many patients, especially those with concomitant anxiety disorders, as well as in the elderly, the tolerability of the drug can be improved if treatment begins with a lower dose than recommended in the instructions for its use. The tolerability of serotonin reuptake inhibitors at the beginning of treatment can be improved by taking the drug with meals.

To start treatment it is convenient to use so-called "start" packages, which are a sample and are given out for free. This relieves patients from the need to purchase a drug that may not be suitable because of intolerable side effects. If the drug has only a partial effect, then, in the absence of serious side effects, its dose can be brought to the upper limit of the therapeutic range.

Typically, in outpatient treatment, in most cases, 4-6 weeks of treatment is sufficient to evaluate the effectiveness of the drug. The individual response of patients to antidepressants varies widely, and, unfortunately, it is impossible to determine in advance whether the effect will be rapid or slower. Scientists conducted a meta-analysis of the results of registration studies of drugs for the treatment of major depression to determine: if the patient did not respond to treatment during the first week, then what is the probability of improvement at week 6 of therapy (6 weeks - the standard duration of treatment in clinical trials of antidepressants). In this study group, it was shown that if improvement did not occur at week 5, then the probability of improvement at week 6 was not higher than in the control group taking placebo.

Other researchers have obtained similar results. In an open trial of the efficacy of fluoxetine in major depression, attempts were made to determine whether the effect at the 2nd, 4th and 6th weeks of treatment could predict the degree of improvement after the 8th week of therapy.

If the antidepressant is ineffective for 6-8 weeks, the following tactic is preferable.

1. Try another antidepressant (not an MAO inhibitor), different from the previous pharmacological properties.
2. Add to the original antidepressant drug lithium or thyroid hormone.
3. Add a second antidepressant.

Other guidelines give similar recommendations, which also assume that the lack of effect requires a change in therapy. According to the recommendations of the APA, if the treatment is unsuccessful, you should switch to another antidepressant with other pharmacological properties or add to the initial second antidepressant. The decision to increase the current therapy or replace the drug is taken depending on the patient's characteristics, the effectiveness of the previous therapy and the experience of the doctor.

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Duration of treatment for depression

After the first episode of major depression, treatment with an antidepressant should usually be continued for 6-12 months, after which the drug is slowly withdrawn for 4-12 weeks or more (depending on the type of drug and dose used). At the stage of continued therapy, the same dose is used, which was effective at the beginning of treatment. After three or more episodes of major depression or two severe episodes, prolonged maintenance therapy is indicated, which also prescribes the administration of an effective dose of an antidepressant.

In the absence of effect, first of all, you should make sure that the treatment is adequate. It is necessary to return to the diagnosis again, paying special attention to the possibility of comorbid disorders (anxiety, dependence on psychotropic substances), unrecognized bipolar disorder or general (somatic or neurological) disease. In elderly patients with the first episode of major depression, it is necessary to carefully exclude somatic disease or iatrogenic conditions (eg, complication of drug therapy), which may be the primary cause of affective symptoms. The ineffectiveness of therapy can also be explained by the low compliance of the patient who is not following the prescribed treatment regimen, or the improper use of the drug (low dose or too short duration of treatment).

As was recommended above, if the initially chosen method of treatment is ineffective, either it is replaced with a new method of treatment, or reinforced by adding additional funds. In the first case, instead of one antidepressant, another is assigned, belonging to the same or to another class, or ECT is performed. Strengthening the effect of the initially prescribed remedy involves attaching the drug with another mechanism of action.

[9], [10], [11]

Changing Depression Therapy

When replacing an antidepressant, you first need to decide whether you should choose a drug from the same class or family or not. The replacement of one TCA by another is successful in 10-30% of cases. When switching from TCAs to heterocyclic antidepressants (more often high doses of trazodone or buspirone), improvement is achieved in 20-50% of cases. The appointment of MAO inhibitors after unsuccessful treatment of TCAs causes an improvement in 65% of patients. When replacing the MAO inhibitor with a serotonin reuptake inhibitor (or vice versa), an adequate washing period is required, the duration of which depends on the half-elutation time of the preparation. Conduction of ECT in patients resistant to TCAs, or replacement of SSRI with TCAs, leads to an improvement in 50-70% of cases. Placebo-controlled studies of the effectiveness of replacing one SSRI were not performed by others, but in open trials the effect was obtained in 26-88% of cases.

With the discontinuation of the serotonin reuptake inhibitor, a kind of "serotonin withdrawal syndrome" may develop. It manifests itself as a malaise, gastrointestinal disorders, anxiety, irritability, and sometimes a feeling of an electric current passing through the arms and legs. This syndrome can develop with a sudden discontinuation of the drug or a miss (by inattention) of one or more doses. The probability of developing the syndrome is inversely proportional to the half-elimination period. Thus, it often occurs with drugs with a short half-eli- mination period (for example, paroxetine or venlafaxine) than drugs with a long half-eli- mination period (eg, fluoxetine). Replacement of one SSRI by another is usually carried out within 3-4 days, but with the appearance of signs of "serotonin withdrawal syndrome" it is produced more slowly. When replacing SSRI with a drug with a different mechanism of action, the transition should always be gradual, since the new drug does not prevent the development of "serotonin withdrawal syndrome".

[12], [13], [14], [15], [16], [17]

Aids for the treatment of depression

With resistance to treatment or incomplete effect, therapy can be strengthened by various means. To enhance the effect of antidepressant, you can add lithium drugs, thyroid hormone (T3), buspirone, stimulants, pindolol. When the effect of SSRIs is inadequate, TCAs are added to it. The most studied two aids - drugs of lithium and T3.

The addition of lithium drugs to TCAs is successful in 40-60% of cases. Improvement may occur within 2-42 days, but in most patients, the effectiveness of therapy can be judged after 3-4 weeks. In a recent double-blind, placebo-controlled study, the efficacy of lithium supplementation was evaluated in 62 patients who underwent a Hamilton depression score after a 6-week treatment with fluoxetine (20 mg / day) or lofepramine (70-210 mg / day) %. Patients were prescribed a lithium drug in a dose that maintains the concentration of lithium in the plasma at a level of 0.6-1.0 meq / l. After 10 weeks, improvement was noted in 15 of 29 (52%) patients taking lithium and antidepressants, and only 8 of 32 (25%) patients taking placebo and antidepressants.

In older patients, lithium appears to be less effective as an adjuvant therapy than in young patients. Zimmer et al. (1991) evaluated the efficacy of lithium as an adjuvant in 15 patients aged 59 to 89 years who had either a 4-week therapy with nortriptyline or was ineffective (n = 14) or had only a partial effect (n = 2). In the course of the study, recovery of euthymia was noted in 20% of patients, partial improvement in 47% of cases.

Predictors of the effectiveness of adjunctive therapy with lithium preparations are bipolar disorder, less severe depression, young age of patients, rapid improvement after the appointment of lithium. In patients who responded to lithium treatment, the probability of a re-episode of depression is lower than in patients who have been resistant to lithium.

Treatment with lithium is usually started at a dose of 300-600 mg / day, then it is corrected so that the concentration of lithium in the plasma is maintained at a level of 0.6-1.0 meq / l. Lithium preparations with slow release of the active substance less often cause side effects. Prior to the appointment of the lithium drug, a laboratory study is needed, as will be discussed later in the discussion of bipolar disorder.

Especially well the possibilities of thyroid hormones are studied when they are added to TCAs. But there are reports that they can also enhance the effect of SSRIs and MAO inhibitors. The efficacy of T3 as an adjuvant therapy has been proven in open and double-blind, controlled studies. Adding T3 to TCAs brings an improvement in 50-60% of cases. It should be emphasized that T 3, rather than T 4, is used as an auxiliary therapy for major depression, since T3 is much more effective. Admission of T4 for hypothyroidism does not prevent the use of T 3 for the treatment of depression. In a study of five of the seven patients with depression who did not respond for 5 weeks to antidepressant treatment, after a T3 dose of 15-50 μg / day, the Hamilton Depression Rating score decreased by more than 50%. Auxiliary therapy T3, as a rule, is well tolerated. Treatment of T3 usually starts with a dose of 12.5-25 μg / day, with severe anxiety the initial dose should be lower. The therapeutic dose ranges from 25 to 50 mcg / day. Against the backdrop of treatment, it is necessary to monitor the function of the thyroid gland, the dose of T3 should be selected in such a way that the secretion of thyroid-stimulating hormone is not suppressed .

As a supportive therapy, a number of other drugs are also used in drug-resistant patients. Most of them were tested only in small open studies.

Buspirone, a partial agonist of 5-HT1D receptors, is used in generalized anxiety disorders. In the study, buspirone was used as an adjuvant in 25 patients with major depression who did not respond to 5-week therapy with SSRIs (fluvoxamine or fluoxetine), and on two or more previous antidepressant treatment regimens. Addition of buspirone in a dose of 20-50 mg / day led to a complete or partial recovery (according to the scale of the overall clinical impression) in 32% and 36% of patients, respectively.

Pindolol - a beta-adrenoreceptor antagonist, used to treat hypertension. In addition, it effectively blocks 5-HT1A receptors. The researchers assigned pindolol 2.5 mg three times a day to eight patients who had not responded to antidepressant treatment for 6 weeks. Five of the eight patients had a rapid improvement within 1 week with a drop in the Hamilton Depression score below 7. But it should be taken into account that preparations of different firms may have different activity, since they differ in the ratio of racemates in the mixture.

Of the other drugs used as auxiliaries, it should be noted psychostimulants (such as methylphenidate, amphetamines, dexedrine), which are used in combination with SSRIs, TCAs and MAO inhibitors. However, when adding a psychostimulant to the MAO inhibitor, care should be taken in view of the danger of increasing blood pressure. When adding TCAs to SSRIs, one should consider the possibility of interaction between TCAs, on the one hand, and paroxetine, sertraline or fluoxetine, on the other hand. With such a combination, a significant increase in TCA concentration in the blood is possible. There are also data on the use of bupropion to enhance the effect of SSRIs. In bipolar affective disorder II tina (BPAR II) during the episode of major depression, the addition of normotimic agents is effective.

[18], [19], [20], [21], [22], [23], [24]