Depression: drugs and psychotherapy

The most commonly used drugs in the treatment of depression are antidepressants . This broad group of drugs has a targeted effect against depression. However, psychotherapeutic methods have proven themselves in the treatment of depression . In acute severe depression, a combination of drug treatment with psychotherapy works best . Psychotherapy and accompanying drug treatment have also proven effective in dysthymia .

What medications are used to treat depression?

In the case of drug treatment , it is important that the doctor and the patient thoroughly discuss it first. The doctor should not only clarify the expected effect of the treatment to the patient, but also warn him of possible side effects . It is always necessary to consider the ratio of benefits and risks. It usually takes about four weeks before the doctor can assess whether the prescribed drug is having the desired effect for the patient [1]. It is important for the patient to come for regular check-ups, because only then will the doctor be able to assess the effectiveness of the treatment and, in the case of taking certain drugs, also perform the necessary control tests (e.g. blood sampling , which will be sent to the laboratory to determine the level of the drugs, or EKG examination ). Depending on the proposed drug, a blood sample (e.g. to examine the blood count , liver and kidney function ) may be taken before starting the treatment.

Antidepressants are sometimes used in combination with so-called antipsychotics , especially in depression with psychotic symptoms (e.g. delusions) or in the depressive phase of bipolar disorder . In certain situations, sedatives can also bring short-term relief , for example, if restlessness and anxiety come to the fore so much that they overshadow other symptoms of depression.

All these drugs interfere with the metabolism of neurotransmitters . These neurotransmitters are in balance in healthy people, but in depressed patients this balance is disturbed. Reduced activity is observed especially for serotonin , noradrenaline and dopamine . These neurotransmitters are found at the synapses of nerve cells in a lower concentration than usual.

Antidepressants

Antidepressants can sometimes be prescribed by a doctor for other mental illnesses , such as anxiety disorders . These drugs increase the availability of neurotransmitters that affect mood, and they interfere with the metabolism inside the brain by the following mechanisms:

• block the reuptake of neurotransmitters from the synaptic cleft to the presynaptic terminal of the nerve cell,
• block the breakdown ( degradation ) of neurotransmitters,
• cause increased release ( secretion ) of neurotransmitters.

In these ways, it is possible to increase the concentration of neurotransmitters and thereby improve the mood of the patient; however, the effect appears only after a longer period of time (often after more than two weeks).

Groups of antidepressants

Antidepressants are divided into several groups [2]:

• selective serotonin reuptake inhibitors ( SSRI ) – prevent serotonin from being transported from the synaptic cleft back into vesicles in the presynaptic terminal of the nerve cell; this makes more serotonin available in the synaptic cleft; examples of SSRIs are citalopram , fluoxetine , etc.;
• Serotonin and noradrenaline reuptake inhibitors ( SNRIs ) – specifically block the reuptake of serotonin and noradrenaline into nerve cells ( neurons ); an example of an SNRI is venlafaxine ;
• noradrenaline and dopamine reuptake inhibitors ( NDRIs ) – these antidepressants specifically block the reuptake of noradrenaline and dopamine into nerve cells (neurons); an example of an NDRI is bupropion ;
• melatonin receptor agonists and 5-HT _{2C receptor} antagonists ( agomelatine ) – melatonin receptor agonists often cause drowsiness; agomelatine additionally blocks 5-HT _2C receptors and therefore has antidepressant effects [3];
• alpha-2-adrenergic receptor antagonists – these drugs block noradrenaline receptors in nerve cells (i.e. the places where the neurotransmitter noradrenaline normally binds) and at the same time increase the secretion of noradrenaline; doctors prescribe them for depressions characterized especially by “inner” restlessness or sleep disorders ;
• non-selective monoamine reuptake inhibitors – this group of drugs includes the so-called tricyclic antidepressants ; today they are no longer the drugs of first choice, as there are other antidepressants that have a more targeted effect (e.g. SSRIs, see above); however, the doctor may prescribe non-selective monoamine reuptake inhibitors in the event that selective drugs do not work for the patient’s depression, or in very severe depression;
• lithium – the mechanism of action of lithium ions has not yet been precisely clarified. Long-term use of lithium helps prevent depressive or manic episodes (see article Bipolar disorder: symptoms and diagnosis ). However, the effects of lithium do not become apparent until several months later. In any case, it is necessary to regularly check the level of lithium in the patient’s blood, as it is a potentially toxic drug that can have serious side effects in too high doses. However, lithium is mainly used in the treatment of bipolar disorder .

Evidence of effectiveness

The effectiveness of antidepressants in mild depressive episodes is not yet sufficiently supported by evidence. Their effectiveness is better documented in moderate and severe depressive episodes [4].

When does treatment need to be adjusted?

If, after four weeks of taking an antidepressant, the patient does not respond to the treatment (i.e. the treatment does not work as it should), it is necessary to clarify the reason why this is so, or to adjust the treatment [5]. Regarding drug treatment, the doctor can choose one of three approaches:

• augmentation – another drug (but not from the antidepressant group) is added to the existing antidepressant; the goal is to improve the effectiveness of an antidepressant;
• change of antidepressant – the doctor prescribes a different antidepressant to the patient; the patient starts taking a “new” antidepressant, on the contrary, stops taking the one originally prescribed;
• a combination of antidepressants – the doctor prescribes a second antidepressant to the patient, usually from a different group (see above, paragraph Groups of antidepressants); the patient then takes both antidepressants.

It is also possible to consider the use of psychotherapy (if it has not been used yet). With drug treatment, the doctor must pay attention to possible drug interactions between the drugs used. In any case, it is necessary to follow the prescribed dose of medication, otherwise the patient’s life may be threatened by the so-called serotonin syndrome [6].

After the patient’s recovery, discontinuation of medication should always take place under the supervision of a doctor, who gradually (over the course of several weeks) reduces the dose. If the patient were to stop the medication earlier than the doctor recommended, the likelihood of relapse (return of the disease) would increase . However, the doctor can also prescribe other drugs to the patient to prevent relapse (so-called maintenance treatment , see the article Depression: Treatment options and prevention of relapse ).