What should one do when the effect of an antidepressant wears off?
In the course of therapy with antidepressants, many patients report a continuous decline in the effect of the respective preparation. This is often due to the fact that many active substances not only have a direct, rapid effect (e.g. increasing the concentration of transmitters in the synaptic cleft) but also lead to various adaptation processes in the brain in the long term. Patients usually report a diminishing antidepressant effect after several weeks or a few months, as the direct and rapid effect increasingly fades.
There are various options for counteracting this development. However, these should always be discussed and agreed with the treating physician. Premature and abrupt discontinuation of a preparation can lead to considerable side effects.
In principle, there are three options available if the effect decreases. With many drugs (including SSRIs), therapy starts with low doses and can be continuously increased over time. In addition, there are many different groups of antidepressant drugs that also have different modes of action.
Depending on the patient, a drug can have different effects. For this reason a change of antidepressant may be indicated. Finally, in certain forms of depression, accompanying psychotherapy can also lead to a considerably improved therapeutic success.
Effect at the synapse
In order to transmit signals, a nerve cell releases different neurotransmitters into the synaptic cleft, which bind to receptors of another nerve cell and transmit the signal. The remaining neurotransmitters are then degraded and reabsorbed into the nerve cells via transporters. A deficiency of the transmitters serotonin and noradrenalin is suspected for the development of depression.
By increasing these transmitter concentrations in the central nervous system, antidepressants have a stimulating and anxiety-reducing effect. The different antidepressants use different approaches and can be classified accordingly. In principle, three different approaches can be distinguished: inhibition of the reuptake of transmitters, inhibition of the degradation of a transmitter and influencing transmitter release by inhibiting receptors on nerve cells.
- Inhibition of transmitter reuptake: Among the drugs that inhibit transmitter reuptake are tricyclic antidepressants (amitryptiline, clomipramine, nortriptyline), selective serotonin reuptake inhibitors (citalopram, fluoxetine), venlafaxine, reboxetine, bupropion and St. John’s wort. These active ingredients lead to increased transmitter concentrations in the synaptic cleft via the inhibited retransport and an associated increased signal transmission. – Inhibition of transmitter degradation: MAO inhibitors (especially moclobemide and tranylcypromine) inhibit various enzymes in the nerve cells, which means that the transmitters are not degraded.
As a result, they are released in higher concentrations. – Influencing transmitter release: Mirtazapine leads to increased release of the transmitters into the synaptic cleft by blocking various receptors of nerve cells responsible for transmitter release. In addition to its antidepressant effect, mirtazapine also has a strong sleep-inducing effect.