38 - References

References

364 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 3 for 4–6 months after remission may be relatively effective at preventing a recurrence in psychotic depression.4 In the UK, NICE15 suggests continuing antipsychotic medication for a number of months after remission, but it is not clear how long combination therapy should be continued past this point. This decision could be based on patient preference and adverse effect profile (e.g. weight gain). Options might include slowly tapering the antipsychotic with reintroduction if psychotic symptoms return or switching to an antipsychotic with different adverse effects. Currently there is no evidence to support the best way to do this. Other treatments Another potential treatment approach is based on glucocorticoid receptor blocking strategies, since hypothalamic–pituitary–adrenal axis hyperactivity is more common in psychotic depression. A combined analysis of data from five double-blind trials (mifepristone n = 833, placebo n = 627) evaluating the efficacy and safety of 7 days’ treatment with mifepristone compared with placebo found that mifepristone reduced psychotic symptoms.29 Patients with a high mifepristone plasma level (≥1637ng/mL) showed a more significant treatment response.29 There is an anecdotal report of the successful use of methylphenidate in a patient who did not respond to robust doses of an antidepressant and antipsychotic combined.30 Other case reports describe successful outcomes with lamotrigine31 and a combination of phenelzine, aripiprazole and quetiapine.32 Minocycline has also shown some effect, albeit in an open study.33 Summary ■ ■In the acute phase of psychotic depression, the combination of an antipsychotic and antidepressant is the best treatment option. The strongest evidence is for a combination of olanzapine and fluoxetine. ■ ■Monotherapy is less effective than combined therapy but if this is the best approach for the patient, TCAs are the drugs of choice. ■ ■If using combined therapy, treat with this combination for at least 4–6 months after remission. After this time, consider slowly tapering the antipsychotic but make a decision based on risk (e.g. metabolic syndrome) and potential benefit (e.g. past history of relapse and psychosis). ■ ■ECT is an effective treatment. Consider when a rapid response is required or where other treatments have failed. ■ ■Ketamine formulations may be effective but are not first-­line agents. References

1. Jääskeläinen E, et al. Epidemiology of psychotic depression: systematic review and meta-­analysis. Psychol Med 2018; 48:905–­918.
2. Heslin M, et al. Psychotic major depression: challenges in clinical practice and research. Br J Psychiatry 2018; 212:131–133.
3. Rothschild AJ, et al. Missed diagnosis of psychotic depression at 4 academic medical centers. J Clin Psychiatry 2008; 69:1293–1296.
4. Coryell WH. Maintenance treatment for psychotic depressive disorders: progress and remaining challenges. JAMA 2019; 322:615–­617.
5. Tohen M, et al. Two-­year outcomes in first-­episode psychotic depression the McLean–Harvard First-­Episode Project. J Affect Disord 2012; 136:1–8.
6. Flint AJ, et al. Two-­year outcome of psychotic depression in late life. Am J Psychiatry 1998; 155:178–183.

Depression and anxiety disorders CHAPTER 3 7. Maj M, et al. Phenomenology and prognostic significance of delusions in major depressive disorder: a 10-­year prospective follow-­up study. J Clin Psychiatry 2007; 68:1411–1417. 8. Paljärvi T, et al. Mortality in psychotic depression: 18-­year follow-­up study. Br J Psychiatry 2023; 222:37-­43. 9. Gaudiano BA, et al. Differential response to combined treatment in patients with psychotic versus nonpsychotic major depression. J Nerv Ment Dis 2005; 193:625–628. 10. Gournellis R, et al. Psychotic (delusional) depression and suicidal attempts: a systematic review and meta-­analysis. Acta Psychiatr Scand 2018; 137:18–29. 11. Kendrick T, et al. Management of depression in adults: summary of updated NICE guidance. BMJ 2022; 378:o1557. 12. Oliva V, et al. Pharmacological treatments for psychotic depression: a systematic review and network meta-­analysis. Lancet Psychiatry 2024; 11:210–220. 13. Kruizinga J, et al. Pharmacological treatment for psychotic depression. Cochrane Database Syst Rev 2021; 12:CD004044. 14. Farahani A, et al. Are antipsychotics or antidepressants needed for psychotic depression? A systematic review and meta-­analysis of trials comparing antidepressant or antipsychotic monotherapy with combination treatment. J Clin Psychiatry 2012; 73:486–496. 15. National Institute for Health and Care Excellence. Depression in adults: treatment and management. NICE guideline [NG222]. 2022 (last updated May 2024, last checked May 2024); https://www.nice.org.uk/guidance/ng222. 16. Gałuszko-­Wȩgielnik M, et al. Central nervous system-­related safety and tolerability of add-­on ketamine to standard of care treatment in treatment-­resistant psychotic depression in patients with major depressive disorder and bipolar disorder. Front Neurosci 2023; 17:1214972. 17. Le TT, et al. Ketamine for psychotic depression: an overview of the glutamatergic system and ketamine’s mechanisms associated with antidepressant and psychotomimetic effects. Psychiatry Res 2021; 306:114231. 18. Beck K, et al. Association of ketamine with psychiatric symptoms and implications for its therapeutic use and for understanding schizophrenia: a systematic review and meta-­analysis. JAMA Netw Open 2020; 3:e204693. 19. Ajub E, et al. Efficacy of esketamine in the treatment of depression with psychotic features: a case series. Biol Psychiatry 2018; 83:e15–e16. 20. Buchan H, et al. Who benefits from electroconvulsive therapy? Combined results of the Leicester and Northwick Park trials. Br J Psychiatry 1992; 160:355–359. 21. Heijnen W, et al. Influence of age on ECT efficacy in depression and the mediating role of psychomotor retardation and psychotic features. J Psychiatr Res 2019; 109:41–-­47. 22. Pinna M, et al. Clinical and biological predictors of response to electroconvulsive therapy (ECT): a review. Neurosci Lett 2018; 669:32–42. 23. Spaans HP, et al. Early complete remitters after electroconvulsive therapy: profile and prognosis. J ECT 2016; 32:82–87. 24. Birkenhager TK, et al. One-­year outcome of psychotic depression after successful electroconvulsive therapy. J ECT 2005; 21:221–226. 25. Wagenmakers MJ, et  al. Psychotic late-­life depression less likely to relapse after electroconvulsive therapy. J Affect Disord 2020; 276:984–990. 26. Navarro V, et al. Continuation/maintenance treatment with nortriptyline versus combined nortriptyline and ECT in late-­life psychotic depression: a two-­year randomized study. Am J Geriatr Psychiatry 2008; 16:498–505. 27. Bingham KS, et al. Stabilization treatment of remitted psychotic depression: the STOP-­PD study. Acta Psychiatr Scand 2018; 138:267–273. 28. Flint AJ, et al. Effect of continuing olanzapine vs placebo on relapse among patients with psychotic depression in remission: the STOP-­PD II randomized clinical trial. JAMA 2019; 322:622–631. 29. Block T, et al. Mifepristone plasma level and glucocorticoid receptor antagonism associated with response in patients with psychotic depression. J Clin Psychopharmacol 2017; 37:505–511. 30. Huang CC, et  al. Adjunctive use of methylphenidate in the treatment of psychotic unipolar depression. Clin Neuropharmacol 2008; 31:245–247. 31. Kajiya T, et al. Effect of lamotrigine in the treatment of bipolar depression with psychotic features: a case report. Ann Gen Psychiatry 2017; 16:31. 32. Meyer JM, et al. Augmentation of phenelzine with aripiprazole and quetiapine in a treatment-­resistant patient with psychotic unipolar depression: case report and literature review. CNS Spectr 2017; 22:391–396. 33. Miyaoka T, et  al. Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-­label study. Prog Neuropsychopharmacol Biol Psychiatry 2012; 37:222–226.