SPRAVATO

• Key points

Favourable opinion for reimbursement in combination with a SSRI or SNRI for the treatment of treatment-resistant major depressive disorder in adults under 65 years of age who have not responded to at least two different treatments with antidepressants in the current severe depressive episode and in the event of contraindication or resistance to electroconvulsive therapy or for patients who do not have access to or have refused this therapy.

Unfavourable opinion for reimbursement in the rest of the MA indication.

• What therapeutic improvement?

No clinical added value in the therapeutic strategy.

• Role in the care pathway?

The treatment of resistant depression requires a specialist opinion and there is no current consensus in the guidelines concerning the therapeutic strategy to be adopted.

National guidelines formalised by the Association Française de Psychiatrie Biologique et Neuropsychopharmacologie (AFPBN - French Association for Biological Psychiatry and Neuropsychopharmacology) and the FondaMental foundation were published in 2017, for example, detailing the therapeutic strategy in the event of a lack of response to antidepressant therapy.

The resistant nature of a major depressive episode must be the subject of in-depth diagnosis by a specialist to rule out any pseudo-resistance and confirm the treatment strategy.

In the event of an inadequate response to first-line treatment, dosage optimisation with an increase in dose or change of antidepressant is recommended.

Augmentation of antidepressant therapy by the addition of lithium salts, triiodothyronine (T3) or antipsychotic medications (aripiprazole, quetiapine), in a context of off-label use, is also a therapeutic option in the event of a partial response to the initial treatment.

Combination with a second antidepressant treatment (in particular, alpha-2 agonists mirtazapine or mianserin) may also be envisaged in the event of a partial response to well-managed initial treatment, at an appropriate time, taking into account the potential interactions and contraindications.

The addition of psychotherapy to antidepressant treatment is also effective in the event of resistant moderate major depressive disorder.

Hospitalisation is recommended in the event of severe major depressive disorder.

In the event of severe treatment-resistant depression, non-medicinal salvage methods exist, such as electroconvulsive therapy or transcranial magnetic stimulation.

Role of the medicinal product in the care pathway:

SPRAVATO (esketamine), in combination with a SSRI or SNRI, is an alternative for the treatment of treatment-resistant major depressive disorder in adults under 65 years of age who have not responded to at least two different treatments with antidepressants in the current severe depressive episode and in the event of contraindication or resistance to electroconvulsive therapy or for patients who do not have access to or have refused this therapy.

In the other clinical situations covered by the MA, SPRAVATO (esketamine) has no role in the therapeutic strategy.

• Special recommendations

Considering the risks of the development of adverse effects during the post-administration period with SPRAVATO 28 mg (esketamine), in particular sedation, dizziness and hypertension, the Committee reiterates that, in accordance with the SmPC, patients must be monitored adequately in the period immediately following the administration, which takes place in a hospital setting only. In particular, blood pressure should be reassessed approximately 40 minutes after administration and the healthcare professional should assess the clinical condition of patients until they are ready to leave the healthcare setting.

The Committee also reiterates the need to administer SPRAVATO (esketamine) in a setting where appropriate resuscitation equipment and healthcare professionals with training in cardiopulmonary resuscitation are available, for any patients with clinically significant or unstable cardiovascular or respiratory conditions (see SmPC).