Psychotic depression, also known asdepressive psychosis, is amajor depressive episode that is accompanied bypsychotic symptoms.[2] It can occur in the context ofbipolar disorder ormajor depressive disorder.[2] Psychotic depression can be difficult to distinguish fromschizoaffective disorder, a diagnosis that requires the presence of psychotic symptoms for at least two weeks without any mood symptoms present.[2] Unipolar psychotic depression requires that psychotic symptoms occur during severe depressive episodes, although residual psychotic symptoms may also be present in between episodes (e.g., during remission, mild depression, etc.).[3][4][5][6][7] Diagnosis using theDSM-5 involves meeting the criteria for a major depressive episode, along with the criteria for "mood-congruent ormood-incongruent psychotic features" specifier.[8]
People with psychotic depression experience the symptoms of a major depressive episode, along with one or more psychotic symptoms, includingdelusions and/orhallucinations.[2] 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.[2] Common themes of mood congruent delusions include guilt,persecution, punishment, personal inadequacy, or disease.[9] Half of patients experience more than one kind of delusion.[2] Delusions occur without hallucinations in about one-half to two-thirds of patients with psychotic depression.[2] Hallucinations can be auditory, visual, olfactory (smell), or tactile (touch), and are congruent with delusional material.[2] Affect is sad, not flat. Severeanhedonia, loss of interest, andpsychomotor retardation are typically present.[10]
Psychotic symptoms tend to develop after an individual has already had several episodes of depression without psychosis.[2] However, once psychotic symptoms have emerged, they tend to reappear with each future depressive episode.[2] Theprognosis for psychotic depression is not considered to be as poor as for schizoaffective disorders or primary psychotic disorders.[2] 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.[2][9]
Family members of those who have experienced psychotic depression are at increased risk for both psychotic depression and schizophrenia.[2][needs update]
Most patients with psychotic depression report having an initial episode between the ages of 20 and 40. 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. People who received appropriate treatment for psychotic depression went into "remission" and have reported a quality of life similar to that of people without PD.[11]
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 thehypothalamic pituitary adrenal axis (HPA). The HPA axis appears to be dysregulated in psychotic depression, withdexamethasone suppression tests demonstrating higher levels ofcortisol following dexamethasone administration (i.e. lower cortisol suppression).[2] Those with psychotic depression also have higherventricular-brain ratios than those with non-psychotic depression.[2]
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.[2] On the other hand, psychotic depression may be confused withschizoaffective disorder.[2] Due to overlapping symptoms, differential diagnosis includes alsodissociative disorders.[12]
Several treatment guidelines recommend pharmaceutical treatments that include either the combination of a second-generation antidepressant and atypical antipsychotic ortricyclic antidepressant monotherapy orelectroconvulsive therapy (ECT) as the first-line treatment for unipolar psychotic depression.[13][14][15][16]
There is some evidence indicating that combination therapy with an antidepressant plus an antipsychotic is more effective in treating psychotic depression than either antidepressant treatment alone or placebo.[17] In the context of psychotic depression, the following are the most well-studied antidepressant/antipsychotic combinations:
There is insufficient evidence to determine if treatment with an antidepressant alone is effective.[17] Tricyclic antidepressants may be particularly dangerous, because overdosing has the potential to cause fatal cardiac arrhythmias.[14]
There is insufficient evidence to determine if treatment with antipsychotic medications alone is effective.[17]Olanzapine may be an effective monotherapy in psychotic depression,[23] although there is evidence that it is ineffective for depressive symptoms as a monotherapy;[14][21] and olanzapine/fluoxetine is more effective.[14][21]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.[24][25][26] The current drug-based treatments of psychotic depression are reasonably effective but can cause side effects, such as nausea, headaches, dizziness, and weight gain.[27]
In modern practice of ECT a therapeutic clonicseizure is induced by electric current via electrodes placed on a person under generalanesthesia. Despite much research the exact mechanism of action of ECT is still not known.[28] ECT carries the risk of temporary cognitive deficits (e.g., confusion, memory problems), in addition to the burden of repeated exposures to general anesthesia.[29]
Efforts are made to find a treatment which targets the proposed specific underlying pathophysiology of psychotic depression. A promising candidate wasmifepristone,[30] which by competitively blocking certain neuro-receptors, renders cortisol less able to directly act on the brain and was thought to therefore correct an overactiveHPA axis. However, a Phase III clinical trial, which investigated the use of mifepristone in PMD, was terminated early due to lack of efficacy.[31]
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:[32] potential precipitating factors,[33][34][35] underlying biology,[36][37][38][39] symptomatology beyond psychotic symptoms,[40][41] long-term prognosis,[42][43] and responsiveness to psychopharmacological treatment and ECT.[44]
^abcdefghijklmnopqHales E and Yudofsky JA, eds, The American Psychiatric Press Textbook of Psychiatry, Washington, DC: American Psychiatric Publishing, Inc., 2003
^Kupfer, D. J., Frank, E., & Phillips, M. L. (2012). Major depressive disorder: New clinical, neurobiological, and treatment perspectives. Lancet, 379(9820), 1045-1055
^Roca et al. (2014). Frequency and predictors of psychotic symptoms in a general population sample. Acta Psychiatrica Scandinavica, 129(4), 286-295
^García-Álvarez et al. (2013). Residual psychotic symptoms in depression: Prevalence and relationship to mood symptoms, anxiety symptoms, and treatment response. Acta Psychiatrica Scandinavica, 128(5), 375-382
^Lennox et al. (2010). Residual psychotic and depressive symptoms in a clinical trial for psychotic depression. Journal of Affective Disorders, 127(1-3), 243-248
^Rothschild, A.J., 2009. Clinical Manual for Diagnosis and Treatment of Psychotic Depression. American Psychiatric Publishing, Inc. Washington DC, USAISBN978-1-58562-292-4
^Shibayama M (2011). "Differential diagnosis between dissociative disorders and schizophrenia".Psychiatria et Neurologia Japonica.113 (9):906–911.PMID22117396.
^abcdeTaylor, David; Patron, Carol; Kapur, Shitij (2012).Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: John Wiley & Sons, Inc. pp. 233–234.ISBN9780470979693.
^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.PMID3883815.
^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.PMID9555596.
^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.PMID15232326.S2CID36295165.
^abcRothschild, 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.PMID15232326.S2CID36295165.
^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.doi:10.1017/S1092852900020307.PMID19668121.S2CID29260337.{{cite journal}}:|first7= has generic name (help)
^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.PMID20691481.
^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.PMID11593077.S2CID3067889.
^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.PMID23147239.S2CID29557858.
^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.PMID23228568.
^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.PMID20951386.
^Nelson, JC; Davis, JM (1997). "DST studies in psychotic depression: A meta-analysis".The American Journal of Psychiatry.154 (11):1497–503.doi:10.1176/ajp.154.11.1497.PMID9356556.
^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.PMID10920463.
^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.PMID10071716.S2CID19469775.
^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.PMID17915981.
^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.PMID22381953.
^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.doi:10.1176/ajp.153.4.483.PMID8599395.
^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.PMID12706521.
