Psychotic depression, also known as depressive psychosis, is a major depressive episode that is accompanied by psychotic symptoms. It can occur in the context of bipolar disorder or major depressive disorder. It can be difficult to distinguish from schizoaffective disorder, a diagnosis that requires the presence of psychotic symptoms for at least two weeks without any mood symptoms present. Conversely, psychotic depression requires that the psychotic features occur only during episodes of major depression. Diagnosis using the DSM-IV involves meeting the criteria for a major depressive episode, along with the criteria for the "psychotic features" specifier.
Individuals with psychotic depression experience the symptoms of a major depressive episode, along with one or more psychotic symptoms, including delusions and/or hallucinations. Delusions can be classified as mood congruent or incongruent, depending on whether or not the nature of the delusions is in keeping with the individual's mood state. Common themes of mood congruent delusions include guilt, punishment, personal inadequacy, or disease. Half of patients experience more than one kind of delusion. Delusions occur without hallucinations in about one-half to two-thirds of patients with psychotic depression. Hallucinations can be auditory, visual, olfactory (smell), or haptic (touch). Severe anhedonia, loss of interest, and psychomotor retardation are typically present.
Psychotic symptoms tend to develop after an individual has already had several episodes of depression without psychosis. However, once psychotic symptoms have emerged, they tend to reappear with each future depressive episode. The prognosis for psychotic depression is not considered to be as poor as for schizoaffective disorders or primary psychotic disorders. Still, those who have experienced a depressive episode with psychotic features have an increased risk of relapse and suicide compared to those without psychotic features, and they tend to have more pronounced sleep abnormalities.
The families of those who have experienced psychotic depression are at increased risk for both psychotic depression and schizophrenia.
Most patients with psychotic depression report having an initial episode between the ages of 20 and 40. Over a lifetime, it appears that patients with psychotic depression experience an average of 4 to 9 episodes. As with other depressive episodes, psychotic depression tends to be episodic, with symptoms lasting for a certain amount of time and then subsiding. While psychotic depression can be chronic (lasting more than 2 years), most depressive episodes last less than 24 months. Unlike psychotic disorders such as schizophrenia and schizoaffective disorder, patients with psychotic depression generally function well between episodes, both socially and professionally.
Psychotic symptoms are often missed in psychotic depression, either because patients do not think their symptoms are abnormal or they attempt to conceal their symptoms from others. On the other hand, psychotic depression may be confused with schizoaffective disorder. Due to overlapping symptoms, differential diagnosis includes also dissociative disorders.
There are a number of biological features that may distinguish psychotic depression from non-psychotic depression. The most significant difference may be the presence of an abnormality in the hypothalamic pituitary adrenal axis (HPA) axis. The HPA axis appears to be dysregulated in psychotic depression, with dexamethasone suppression tests demonstrating higher levels of cortisol following dexamethasone administration (i.e. lower cortisol suppression). Those with psychotic depression also have higher ventricular-brain ratios than those with non-psychotic depression.
Several treatment guidelines recommend either the combination of a second-generation antidepressant and atypical antipsychotic or tricyclic antidepressant monotherapy or electroconvulsive therapy (ECT) as the first-line treatment for unipolar psychotic depression.
Pharmaceutical treatments can include tricyclic antidepressants, atypical antipsychotics, or a combination of an antidepressant from the newer, more well tolerated SSRI or SNRI categories and an atypical antipsychotic. Olanzapine may be an effective monotherapy in psychotic depression, although there is evidence that it is ineffective for depressive symptoms as a monotherapy; and olanzapine/fluoxetine is more effective. Quetiapine monotherapy may be particularly helpful in psychotic depression since it has both antidepressant and antipsychotic effects and a reasonable tolerability profile compared to other atypical antipsychotics. The current drug-based treatments of psychotic depression are reasonably effective but can cause side effects, such as nausea, headaches, dizziness, and weight gain. Tricyclic antidepressants are particularly dangerous in overdose due to their potential to cause potentially-fatal cardiac arrhythmias.
In the context of psychotic depression, the following are the most well-studied antidepressant/antipsychotic combinations
In modern practice of ECT a therapeutic clonic seizure is induced by electric current via electrodes placed on an anaesthetised, unconscious patient. Despite much research the exact mechanism of action of ECT is still not known. ECT carries the risk of temporary cognitive deficits (e.g., confusion, memory problems), in addition to the burden of repeated exposures to general anesthesia.
Among the newer experimental treatments is the study of glucocorticoid antagonists, including mifepristone. These strategies may treat the underlying pathophysiology of psychotic depression by correcting an overactive HPA axis. By competitively blocking certain neuro-receptors, these medications render cortisol less able to directly act on the brain.
Mifepristone showed initial promise in psychotic major depression, a form of depression that is difficult to treat; however, a Phase III clinical trial was terminated early due to lack of efficacy.
Transcranial magnetic stimulation (TMS) is being investigated as an alternative to ECT in the treatment of depression. TMS involves the administration of a focused electromagnetic field to the cortex to stimulate specific nerve pathways.
Research has shown that psychotic depression differs from non-psychotic depression in a number of ways: potential precipitating factors, underlying biology, symptomatology beyond psychotic symptoms, long-term prognosis, and responsiveness to psychopharmacological treatment and ECT.
The long-term outcome for psychotic depression is generally poorer than for non-psychotic depression.
- Hales E and Yudofsky JA, eds, The American Psychiatric Press Textbook of Psychiatry, Washington, DC: American Psychiatric Publishing, Inc., 2003
- "Unipolar major depression with psychotic features: Epidemiology, clinical features, assessment, and diagnosis". www.uptodate.com. Retrieved 2016-05-29.
- American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington DC: American Psychiatric Association. ISBN 978-0890420256.
- Practice Guideline for the Treatment of Patients with Major Depressive Disorder. APA Practice Guidelines (3rd ed.) (American Psychiatric Association). doi:10.1176/appi.books.9780890423387.654001. Retrieved April 6, 2013.
- Rothschild, A.J., 2009. Clinical Manual for Diagnosis and Treatment of Psychotic Depression. American Psychiatric Publishing, Inc. Washington DC, USA ISBN 978-1-58562-292-4
- Shibayama M (2011). "Differential diagnosis between dissociative disorders and schizophrenia". Psychiatria et neurologia Japonica 113 (9): 906–911. PMID 22117396.
- "Somatic Treatment of an Acute Episode of Unipolar Psychotic Depression". WebMD LLC. 2013. Retrieved 4 October 2013.
- Taylor, David; Patron, Carol; Kapur, Shitij (2012). Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: John Wiley & Sons, Inc. pp. 233–234. ISBN 9780470979693.
- Wijkstra, J; Lijmer, J; Balk, FJ; Geddes, JR; Nolen, WA (2006). "Pharmacological treatment for unipolar psychotic depression: Systematic review and meta-analysis" (PDF). British Journal of Psychiatry 188 (5): 410–5. doi:10.1192/bjp.bp.105.010470. PMID 16648526.
- Leadholm, Anne Katrine K.; Rothschild, Anthony J.; Nolen, Willem A.; Bech, Per; Munk-Jørgensen, Povl; Ostergaard, Søren Dinesen (2013). "The treatment of psychotic depression: Is there consensus among guidelines and psychiatrists?". Journal of Affective Disorders 145 (2): 214–20. doi:10.1016/j.jad.2012.07.036. PMID 23021823.
- Schatzberg, AF (2003). "New approaches to managing psychotic depression" (PDF). The Journal of Clinical Psychiatry. 64 Suppl 1: 19–23. PMID 12625801.
- Rothschild, Anthony J.; Williamson, Douglas J.; Tohen, Mauricio F.; Schatzberg, Alan; Andersen, Scott W.; Van Campen, Luann E.; Sanger, Todd M.; Tollefson, Gary D. (August 2004). "A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features". The Journal of Clinical Psychopharmacology 24 (4): 365–373. doi:10.1097/01.jcp.0000130557.08996.7a. PMID 15232326.
- Weisler, R; Joyce, M; McGill, L; Lazarus, A; Szamosi, J; Eriksson, H; Moonstone Study, Group (2009). "Extended release quetiapine fumarate monotherapy for major depressive disorder: Results of a double-blind, randomized, placebo-controlled study". CNS spectrums 14 (6): 299–313. PMID 19668121.
- Bortnick, Brian; El-Khalili, Nizar; Banov, Michael; Adson, David; Datto, Catherine; Raines, Shane; Earley, Willie; Eriksson, Hans (2011). "Efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in major depressive disorder: A placebo-controlled, randomized study". Journal of Affective Disorders 128 (1–2): 83–94. doi:10.1016/j.jad.2010.06.031. PMID 20691481.
- Maneeton, Narong; Maneeton, Benchalak; Srisurapanont, Manit; Martin, Stephen D (2012). "Quetiapine monotherapy in acute phase for major depressive disorder: A meta-analysis of randomized, placebo-controlled trials". BMC Psychiatry 12: 160. doi:10.1186/1471-244X-12-160. PMC 3549283. PMID 23017200.
- Mayo Clinic http://www.mayoclinic.com/health/antidepressants/MH00062
- Spiker, DG; Weiss, JC; Dealy, RS; Griffin, SJ; Hanin, I; Neil, JF; Perel, JM; Rossi, AJ; Soloff, PH (1985). "The pharmacological treatment of delusional depression". American Journal of Psychiatry 142 (4): 430–436. doi:10.1176/ajp.142.4.430. PMID 3883815.
- Muller-Siecheneder, Florian; Muller, Matthias J.; Hillert, Andreas; Szegedi, Armin; Wetzel, Hermann; Benkert, Otto (1998). "Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome". The Journal of Clinical Psychopharmacology 18 (2): 111–120. doi:10.1097/00004714-199804000-00003. PMID 9555596.
- Rothschild, Anthony J.; Williamson, Douglas J.; Tohen, Mauricio F.; Schatzberg, Alan; Andersen, Scott W.; Van Campen, Luann E.; Sanger, Todd M.; Tollefson, Gary D. (2004). "A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features". The Journal of Clinical Psychopharmacology 24 (2): 365–373. doi:10.1097/01.jcp.0000130557.08996.7a. PMID 15232326.
- Meyers, BS; Flint, AJ; Rothschild, AJ; Mulsant, BH; Whyte, EM; Peasley-Miklus, C; Papademetriou, E; Leon, AC; Heo, M; Stop-Pd, Group (August 2009). "A double-blind randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD)". Archives of General Psychiatry 66 (8): 838–847. doi:10.1001/archgenpsychiatry.2009.79. PMC 2840400. PMID 19652123.
- Bolwig, T. (2011). "How does electroconvulsive therapy work? Theories on its mechanism". The Canadian Journal of Psychiatry 51 (1): 13–18. PMID 21324238.
- "Electroconvulsive therapy (ECT): Risks". MayoClinic.com. 2012-10-25. Retrieved 2013-10-04.
- Belanoff, Joseph K.; Flores, Benjamin H.; Kalezhan, Michelle; Sund, Brenda; Schatzberg, Alan F. (October 2001). "Rapid reversal of psychotic depression using mifepristone". Journal of Clinical Psychopharmacology 21 (5): 516–21. doi:10.1097/00004714-200110000-00009. PMID 11593077.
- Mifepristone#cite ref-20
- Ostergaard, SD; Rothschild, AJ; Uggerby, P; Munk-Jørgensen, P; Bech, P; Mors, O (2012). "Considerations on the ICD-11 classification of psychotic depression". Psychotherapy and psychosomatics 81 (3): 135–44. doi:10.1159/000334487. PMID 22398817.
- Østergaard, Søren Dinesen; Petrides, Georgios; Dinesen, Peter Thisted; Skadhede, Søren; Bech, Per; Munk-Jørgensen, Povl; Nielsen, Jimmi (2013). "The Association between Physical Morbidity and Subtypes of Severe Depression". Psychotherapy and Psychosomatics 82 (1): 45–52. doi:10.1159/000337746. PMID 23147239.
- Østergaard, Søren Dinesen; Waltoft, Berit Lindum; Mortensen, Preben Bo; Mors, Ole (2013). "Environmental and familial risk factors for psychotic and non-psychotic severe depression". Journal of Affective Disorders 147 (1–3): 232–40. doi:10.1016/j.jad.2012.11.009. PMID 23228568.
- Domschke, Katharina; Lawford, Bruce; Young, Ross; Voisey, Joanne; Morris, C. Phillip; Roehrs, Tilmann; Hohoff, Christa; Birosova, Eva; Arolt, Volker; Baune, Bernhard T. (2011). "Dysbindin (DTNBP1) – A role in psychotic depression?". Journal of Psychiatric Research 45 (5): 588–95. doi:10.1016/j.jpsychires.2010.09.014. PMID 20951386.
- Nelson, JC; Davis, JM (1997). "DST studies in psychotic depression: A meta-analysis". The American Journal of Psychiatry 154 (11): 1497–503. PMID 9356556.
- Posener, JA; Debattista, C; Williams, GH; Chmura Kraemer, H; Kalehzan, BM; Schatzberg, AF (2000). "24-Hour monitoring of cortisol and corticotropin secretion in psychotic and nonpsychotic major depression". Archives of General Psychiatry 57 (8): 755–60. doi:10.1001/archpsyc.57.8.755. PMID 10920463.
- Cubells, JF; Price, LH; Meyers, BS; Anderson, GM; Zabetian, CP; Alexopoulos, GS; Nelson, JC; Sanacora, G; Kirwin, P; Carpenter, L; Malison, RT; Gelernter, J (2002). "Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression". Biological Psychiatry 51 (5): 358–64. doi:10.1016/S0006-3223(01)01349-X. PMID 11904129.
- Meyers, BS; Alexopoulos, GS; Kakuma, T; Tirumalasetti, F; Gabriele, M; Alpert, S; Bowden, C; Meltzer, HY (1999). "Decreased dopamine beta-hydroxylase activity in unipolar geriatric delusional depression". Biological Psychiatry 45 (4): 448–52. doi:10.1016/S0006-3223(98)00085-7. PMID 10071716.
- Maj, M; Pirozzi, R; Magliano, L; Fiorillo, A; Bartoli, L (2007). "Phenomenology and prognostic significance of delusions in major depressive disorder: A 10-year prospective follow-up study". The Journal of Clinical Psychiatry 68 (9): 1411–7. doi:10.4088/JCP.v68n0913. PMID 17915981.
- Østergaard, SD; Bille, J; Søltoft-Jensen, H; Lauge, N; Bech, P (2012). "The validity of the severity-psychosis hypothesis in depression". Journal of Affective Disorders 140 (1): 48–56. doi:10.1016/j.jad.2012.01.039. PMID 22381953.
- Coryell, W; Leon, A; Winokur, G; Endicott, J; Keller, M; Akiskal, H; Solomon, D (1996). "Importance of psychotic features to long-term course in major depressive disorder". The American Journal of Psychiatry 153 (4): 483–9. PMID 8599395.
- Ostergaard, SD; Bertelsen, A; Nielsen, J; Mors, O; Petrides, G (2013). "The association between psychotic mania, psychotic depression and mixed affective episodes among 14,529 patients with bipolar disorder". Journal of Affective Disorders 147 (1–3): 44–50. doi:10.1016/j.jad.2012.10.005. PMID 23122529.
- Birkenhäger, TK; Pluijms, EM; Lucius, SA (2003). "ECT response in delusional versus non-delusional depressed inpatients". Journal of Affective Disorders 74 (2): 191–5. doi:10.1016/S0165-0327(02)00005-8. PMID 12706521.