CHMP评估报告Valdoxan

Major Depressive Disorder (MDD) is reported to be the most common mood disorder, with a lifetime prevalence of about 15% and as high as 25% in women. Despite the availability of effective treatments, many persons with depressive disorders are disabled, and risk of suicide is considerable. Depressive disorders tend to be chronic and both relapse and recurrence are seen frequently. A number of options are currently available for the treatment of MDD, including psychological therapies such as cognitive behavioural therapy and psychoanalytic psychotherapy, antidepressant medications, and electro-convulsive therapy. Initial treatment objectives in the treatment of depression include: 1) Symptom remission (acute phase), 2) Prevention of relapse (continuation phase) and 3) Prevention of recurrences, or new episodes in patients with recurrent depressions (maintenance phase). The presumed mechanism of action of the majority of antidepressants in the treatment of MDD is thought to be via inhibition of neuronal reuptake of monoamines (mainly serotonin and noradrenaline), with a resultant increase in monoamine neurotransmission in the central nervous system (CNS). The major classes of medicinal products used to treat depression are the tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs, e.g., fluoxetine and sertraline), selective noradrenaline reuptake inhibitors (NRIs, e.g. reboxetine), serotonin and noradrenaline reuptake inhibitors (SNRIs, e.g. venlafaxine, duloxetine), heterocyclics (e.g., bupropion), monoamine oxidase (MAO) inhibitors, and a few other compounds such as mirtazapine and mianserin. No single antidepressant medication is clearly more effective than another and no single medication results in remission for all patients. In many occasions the choice of the medication is made looking at the side effect profile. A significant percentage of patients develop sexual side effects after several weeks or months of SSRI and SNRI therapy, especially a decreased ability to have an orgasm. In addition, these medicinal products exert a negative influence on paradoxical sleep, thereby modifying sleep architecture in treated patients. A withdrawal syndrome may also occur upon cessation of treatment. Another inconvenience with SSRIs and SNRIs are that they are generally considered to be less potent than tricyclics for the treatment of severe depression. Furthermore, with all antidepressant drugs currently available, only 60-70% of depressed patients improve. Finally, another major limitation in the therapeutic value of MAOIs, tricyclics as well as SSRIs and SNRIs is the 3-4 weeks latency which unavoidably elapses from starting treatment with any one among these medicinal products to appearance of the first convincing signs of clinical improvement. This delay in their therapeutic efficacy is often a difficult period for the clinician to manage because of the behavioural disinhibition that these medicinal products can induce before raising mood. In particular, for depressed patients with suicidal ideas, suicide attempts can actually occur during the very first weeks of antidepressant treatment. For all these reasons, it is obvious that there is still a need for new antidepressants which would preserve the quality of life and whose therapeutic action would be more efficient than that of medicinal products currently available.