Ten years of maintenance treatment of severe melancholic depression in an adult woman including discontinuation experiences

Abstract

Background There are only few publications on long-term treatments for major depressive disorder (MDD) lasting 5 years or longer. Most clinical controlled trials lasted no longer than 2 years and some recent studies suggested an advantage of cognitive behavioral therapy (CBT) over antidepressants in relapse prevention of MDD.

Methods Exclusively outpatient "real world" treatment of severe melancholia, prospectively documented over 10 years with different serial treatment strategies, discontinuation phenomena and complications.

Methods Compared to CBT, agomelatine, mirtazapine, bupropion and high-dose milnacipran, high-dose venlafaxine (extended-release form, XR) was effective, even sustainably. Asymptomatic premature ventricular contractions (PVCs) were found at the beginning of the treatment of the MDD, which initially led to the discontinuation of high-dose venlafaxine (300 mg daily). Even the various treatment strategies mentioned above were unable to compensate for or prevent the subsequent severe deterioration in MDD (2 rebounds, 1 recurrence). Only the renewed use of high-dose venlafaxine was successful. PVC no longer occurred and the treatment was also well tolerated over the years, with venlafaxine serum levels at times exceeding 5 times the recommended upper therapeutic reference level (known bupropion-venlafaxine interaction, otherwise 2.5 to 3-fold increase with high-dose venlafaxine alone). During dose reduction or after gradual discontinuation of high-dose venlafaxine, rather mild withdrawal symptoms occurred, but as described above, also two severe rebounds and one severe recurrence happened.

Discussion This long-term observation supports critical reflections on the discontinuation of successful long-term treatment with antidepressants in severe MDD, even if it should be under "the protection" of CBT. The PVC seemed to be more related to the duration of the severe major depressive episode than to the venlafaxine treatment itself. A particular prospective observation of this longitudinal case study is that relapses (in the sense of rebounds) during or after previous venlafaxine tapering seemed to herald the recurrence after complete recovery. Remarkably, neither relapses nor recurrence could be prevented by CBT.

Conclusion In this case, high-dose venlafaxine has a particular relapse-preventive (and "recurrence-preventive") effect with good long-term tolerability.

Zusammenfassung

Hintergrund Es gibt kaum Publikationen über Langzeitbehandlungen von schweren rezidivierenden depressiven Episoden (MDD), die einen Zeitraum von 5 Jahren oder länger umfassen. Die meisten klinischen kontrollierten Studien dauerten nicht länger als 2 Jahre und einige neuere Studien deuteten einen Vorteil der kognitiven Verhaltenstherapie (CBT) gegenüber Antidepressiva in der Rückfallprophylaxe der MDD an.

Methode Ausschließlich ambulante „Real world“ Behandlung einer schweren Melancholie, prospektiv dokumentiert über 10 Jahre mit verschiedenen serielle Behandlungsstrategien, Absetzphänomenen und Komplikationen.

Resultate Im Vergleich zur CBT, Agomelatin, Mirtazapin, Bupropion und hoch dosiertem Milnacipran war hoch-dosiertes Venlafaxin (verlängerte Freisetzungsform, XR) wirksam, auch nachhaltig. In der Anfangszeit der Behandlung der schweren depressiven Episode wurden asymptomatische ventrikuläre Extrasystolen (englisch: premature ventricular contractions, PVC) gefunden, was zunächst zum Absetzen von hoch-dosiertem Venlafaxin (täglich 300 mg) führte. Alle oben genannten verschiedenen Behandlungsstrategien konnten die folgenden schweren Verschlechterungen der MDD (2 Rebounds, 1 Rezidiv) nicht kompensieren oder verhindern. Nur der erneute Einsatz von hoch-dosiertem Venlafaxin war erfolgreich. PVC traten nicht mehr auf und die Behandlung wurde auch über die Jahre gut toleriert, wobei der Venlafaxin-Serumspiegel zeitweise das 5-fache des empfohlenen oberen therapeutischen Referenzwertes überstieg (bekannte Bupropion-Venlafaxin-Interaktion; sonst unter hoch-dosiertem Venlafaxin etwa 2,5–3 fach erhöht). Nach Dosisreduktion oder ausschleichendem Absetzen von hoch-dosiertem Venlafaxin kam es zu eher milden Entzugssymptomen, jedoch wie oben beschrieben zu zwei Rebounds und einem Rezidiv (Recurrence).

Diskussion Diese Langzeitbeobachtung unterstützt kritische Reflexionen über den Abbruch erfolgreicher Langzeit-Behandlungen mit AD bei schwerer MDD, auch wenn diese unter „dem Schutz“ einer CBT stehen sollte. Die PVC schienen eher mit der Dauer der schweren depressiven Episode zusammenzuhängen als mit der Venlafaxin-Behandlung. Eine besondere prospektive Beobachtung dieser Längsschnitt-Fallstudie ist, dass die Rückfälle (im Sinne von Rebounds) während oder nach früheren Venlafaxin-Ausschleichmaßnahmen das spätere Rezidiv nach kompletter Genesung anzukündigen schienen. Bemerkenswerterweise konnten weder die Rückfälle noch das Rezidiv mit Hilfe der CBT verhindert werden.

Schlussfolgerung Hochdosiertes Venlafaxin hat in diesem Fall eine besondere rückfallpräventive (und „rezidivpräventive“) Wirkung bei guter Langzeit-Verträglichkeit

Keywords

melancholia - high-dosed milnacipran - antidepressants - relapse prevention - high-dose venlafaxine - therapeutic drug monitoring

Schlüsselwörter

Melancholie - hochdosiertes Milnacipran - hochdosiertes Venlafaxin - Antidepressiva - Rezidivprophylaxe - Therapeutisches Drug Monitoring

Publication History

Received: 19 June 2022

Accepted after revision: 16 May 2024

Article published online:
20 June 2024

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