Treatment Of Psychotic Depression Research Articles

Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.

Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations areassociated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.

Real-world effectiveness of antidepressants and antipsychotics in treatment of psychotic depression

Real-world effectiveness of antidepressants and antipsychotics in treatment of psychotic depression

Sustaining Remission of Psychotic Depression: The STOP-PD II Study Treatment Risks and Benefits in Late Life

Psychotic depression (PD) is a severe disorder that may be more common among the older vs. younger adults. The significant morbidity and disability associated with acute episodes of PD can be especially prominent in the elderly. Treatment guidelines recommend either electroconvulsive therapy or the combination of antidepressant and antipsychotic medications for the acute treatment of PD. However, little is known about the risks and benefits of antipsychotic medication during continuation and maintenance treatment. Premature discontinuation of antipsychotic medication carries the potential risk of early relapse of a severe and potentially lethal disorder. Conversely, the continuation of antipsychotic medication can expose a patient to known adverse effects, such as weight gain and metabolic disturbance, extrapyramidal symptoms and potential impact on brain structure and connectivity. For this symposium, we will first review the epidemiology of PD, its clinical presentation, diagnostic challenges, as well as controversies in treatment with special emphasize on the difference between older vs. younger patients. Then, we will report the results of a NIMH-funded, multicenter randomized placebo-controlled trial (STOP-PD II) that assessed the risks and benefits of continuing antipsychotic medication in 126 adults with PD once the episode of depression had responded to treatment with an antidepressant (sertraline) and an antipsychotic (olanzapine). Notably, 42.9% (n=54) of study participants were aged 60+ years. Finally, we will present the findings of a separate NIMH-funded study that examined the effects of olanzapine vs. placebo on brain structure and connectivity in a subset of STOP-PD II participants using magnetic resonance imaging – this is the first placebo-controlled RCT to examine the effects of antipsychotic medication on brain structure and connectivity in humans. For both studies, differences in outcomes between older adults and younger adults will be highlighted.

SUSTAINING REMISSION OF PSYCHOTIC DEPRESSION: THE STOP-PD II STUDY TREATMENT RISKS AND BENEFITS IN LATE LIFE

Psychotic depression (PD) is a severe disorder that may be more common among the older vs. younger adults. The significant morbidity and disability associated with acute episodes of PD can be especially prominent in the elderly. Treatment guidelines recommend either electroconvulsive therapy or the combination of antidepressant and antipsychotic medications for the acute treatment of PD. However, little is known about the risks and benefits of antipsychotic medication during continuation and maintenance treatment. Premature discontinuation of antipsychotic medication carries the potential risk of early relapse of a severe and potentially lethal disorder. Conversely, the continuation of antipsychotic medication can expose a patient to known adverse effects, such as weight gain and metabolic disturbance, extrapyramidal symptoms and potential impact on brain structure and connectivity. For this symposium, we will first review the epidemiology of PD, its clinical presentation, diagnostic challenges, as well as controversies in treatment with special emphasize on the difference between older vs. younger patients. Then, we will report the results of a NIMH-funded, multicenter randomized placebo-controlled trial (STOP-PD II) that assessed the risks and benefits of continuing antipsychotic medication in 126 adults with PD once the episode of depression had responded to treatment with an antidepressant (sertraline) and an antipsychotic (olanzapine). Notably, 42.9% (n=54) of study participants were aged 60+ years. Finally, we will present the findings of a separate NIMH-funded study that examined the effects of olanzapine vs. placebo on brain structure and connectivity in a subset of STOP-PD II participants using magnetic resonance imaging – this is the first placebo-controlled RCT to examine the effects of antipsychotic medication on brain structure and connectivity in humans. For both studies, differences in outcomes between older adults and younger adults will be highlighted.

Is antidepressant or antipsychotic medication better for the treatment of psychotic depression?

Is antidepressant or antipsychotic medication better for the treatment of psychotic depression?

Advances in the Treatment of Psychotic Depression

Our aim was to update the current understanding of effective treatment strategies for major depression with psychotic features (MDPSY). Most treatment guidelines recommend either the combination of an antidepressant with an antipsychotic or electroconvulsive therapy (ECT) for the treatment of an acute episode of MDPSY. The optimal maintenance treatment after a person responds to either the antidepressant/antipsychotic combination or ECT is unclear particularly as it pertains to length of time the patient needs to take the antipsychotic medication. Further investigation into possible uses of ketamine, lithium carbonate, mifepristone, minocycline, and rTMS may produce possible new treatments in the future. Unfortunately, there is no FDA-approved treatment for MDPSY. The combination of an antidepressant and antipsychotic is significantly more effective than either antidepressant monotherapy or antipsychotic monotherapy for the acute treatment of MDPSY.

Poster Number: EI 13 - Continuation Treatment of Remitted Psychotic Depression: The STOP-PD Study

Introduction: Psychotic depression (PD) is a severe disorder with high levels of morbidity and mortality. It is particularly relevant to the geriatric population, occurring in up to 45% of depressed elderly inpatients. Treatment guidelines recommend either electroconvulsive therapy (ECT) or the combination of antidepressant and antipsychotic medications as acute treatment. There are, however, few data pertaining to the efficacy and tolerability of continuation treatment of PD. Some naturalistic studies report a high frequency of relapse of PD, which may be partly explained by switching from acute ECT to continuation pharmacotherapy; in prospective open-label studies, when PD patients are continued on the treatment that is associated with remission the rate of relapse is lower. Given the paucity of research in this area, we conducted a 12-week double-blind study of continuation pharmacotherapy in persons who had experienced remission of PD in a double-blind RCT comparing the efficacy and tolerability of olanzapine plus sertraline (combination therapy) with olanzapine plus placebo (monotherapy) in adults aged 18 years and older (the STOP-PD study). The specific aims of this continuation study were to examine whether combination therapy and monotherapy differed in: i) stability of remission of depressive and psychotic symptoms; ii) frequency of relapse; and iii) course of weight, serum lipids, and serum glucose. Given the predominantly older age of participants, we examined whether there was an interaction between age, treatment, and outcome.

Síndrome serotoninérgica associada a uso de sertralina: relato de caso

Relato de caso de síndrome serotoninérgica em paciente que iniciou uso de sertralina em dose maior do que o dobro do recomendado para o tratamento de depressão psicótica. Apresentou contratura de membros, olhar perplexo, mutismo e pressão arterial (PA) de 230 x 110 mmHg. A síndrome é cada vez mais comum, mas não é bem reconhecida. Muitos medicamentos podem causá-la e deve-se considerar essa possibilidade em pacientes em uso de medicamentos serotoninérgicos que se apresentam com distúrbios autonômicos ou mentais e sintomas neurológicos. Os achados de clonus, crise oculógira, hiper-reflexia e hipertonicidade devem levar à revisão da medicação. O tratamento centra-se na cessação de agentes causadores, tratamento da possível hipertermia e uso de benzodiazepínicos para diminuir a hipertonia e a excitabilidade neurológica.

SSRI-antipsychotic combination in psychotic depression: sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study.

We recently reported an unexpected interaction between olanzapine and sertraline in a population being treated for psychotic depression. Contrary to knowledge of cytochrome p450 interactions sertraline increased apparent clearance of olanzapine by 30%. Here we examined the pharmacokinetics of sertraline in the same population. Existing studies suggest that sertraline apparent clearance is significantly increased in male subjects and suggested an age/sex interaction. We studied subjects undergoing combination of sertraline/olanzapine treatment for psychotic depression in the Study of the Pharmacotherapy of Psychotic Depression. Nonlinear mixed effect modelling software was used to examine the sertraline pharmacokinetics, evaluating age, sex, race, and olanzapine exposure as covariates. Eighty-seven subjects (median age 62 years, 28 male subjects, 11 African-Americans) provided 138 samples for sertraline concentration. Olanzapine exposure had a 14.8-fold range. A one compartment model with combined residual error described the sertraline concentration data adequately. Half-life and sex effect on sertraline apparent clearance (males averaging 50% higher (p < 0.005); 96.6 l/h vs 64.8 in female subjects) were similar to previous reports. No other covariate (age, race or olanzapine exposure) had a significant impact on apparent clearance, and no age/sex interaction emerged. Sertraline pharmacokinetics were similar to historical descriptions in populations not taking antipsychotics. Unlike our unexpected finding that sertraline increases olanzapine apparent clearance, olanzapine exposure had no impact on sertraline pharmacokinetics. Copyright © 2016 John Wiley & Sons, Ltd.

Odds and ends in psychopharmacology from the past 10 years.

Seven topics previously described in this column are revisited. The use of quantitative electroencephalography has been shown in a prospective study to be effective for predicting antidepressant treatment response. A novel antidepressant drug, agomelatine, has generated much controversy, and its development for the U.S. market was discontinued. A long awaited revised system for categorizing the safety of medications during pregnancy and lactation has finally been published by the Food and Drug Administration. Dextromethorphan/quinidine, eslicarbazepine acetate, levomilnacipran, and esketamine are recent examples of drugs that were developed based on the complex concepts of chirality and stereochemistry. Lisdexamfetamine, a stimulant drug, failed to show benefit as an augmentation therapy for the treatment of depression. The combination drug naltrexone/bupropion was finally approved as a therapy for obesity, after its cardiovascular safety was confirmed in a prospective premarketing study. Further development of the glucocorticoid receptor antagonist drug mifepristone as a treatment for psychotic depression was stopped based on a large negative trial, but the drug continues to be investigated for other potential psychiatric indications. These examples illustrate how the field of psychopharmacology continues to evolve.

Quetiapine in the treatment of psychotic depression: A pilot study

Quetiapine in the treatment of psychotic depression: A pilot study

The treatment of psychotic depression: Is there consensus among guidelines and psychiatrists?

BackgroundPsychotic depression (PD) is a prevalent, severe, under-diagnosed and often inadequately treated mental disorder, which has received disproportionally little attention by clinicians, researchers and the pharmaceutical industry. Consequently, the evidence base for optimal clinical practice regarding PD is limited. The aim of this study was to investigate the degree of consensus among international treatment guidelines on PD and to determine whether a potential lack of consensus would be reflected in the clinical practice of Danish psychiatrists. Methods1.Review and comparison of international guidelines on the treatment of PD.2.Questionnaire based survey regarding Danish psychiatrists’ treatment of PD. ResultsThe nine international treatment guidelines considered in the review have contrasting opinions on the optimal treatment for PD: 6 of 9 suggest antidepressant (AD)+antipsychotic (AP) combination therapy, 3 of 9 recommend AD monotherapy and 5 of 9 find electroconvulsive therapy (ECT) equally appropriate as first line treatment. The 113 surveyed psychiatrists displayed the same lack of consensus. Their preferred treatment was either AD+AP combination therapy (42%), AD monotherapy (31%) or ECT (21%). The first line choices of ADs and APs were tricyclic antidepressants (51%) and quetiapine (62%), respectively. LimitationsThe survey data are subjected to a potential selection bias as the respondents are likely to represent the more informed fraction of psychiatrists. ConclusionsOur results indicate that both treatment algorithms and clinical practice regarding PD are highly heterogeneous. This finding emphasizes the need for further studies on the treatment of psychotic depression.

Treatment of Psychotic Depression in the Elderly Compared With Nonpsychotic Depression

Treatment of Psychotic Depression in the Elderly Compared With Nonpsychotic Depression

Drs. Nelson and Papakostas Reply

Drs. Nelson and Papakostas Reply

Treatment of unipolar psychotic depression

Treatment of unipolar psychotic depression

Misdiagnoses Common in Cases of Depression With Psychosis

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessMisdiagnoses Common in Cases of Depression With PsychosisJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:3 Oct 2008https://doi.org/10.1176/pn.43.19.0020The diagnosis of major depression with psychotic features is often missed in patients, especially in the emergency room, a study reported in the August Journal of Clinical Psychiatry pointed out.The study, which was headed by Anthony Rothschild, M.D., chair of psychiatry at the University of Massachusetts, included 65 inpatients at four academic medical centers. Subjects were recruited from a larger study called the National Institute of Mental Health Study of Pharmacotherapy of Psychotic Depression (STOP-PD), and STOP-PD researchers had determined that all of them had psychotic depression.Moreover, to be in their study, Rothschild explained to Psychiatric News, “all subjects were required to have at least one delusion, and some also had hallucinations. The delusions were most typically somatic delusions, paranoid delusions, delusions of guilt, delusions of poverty, and nihilistic delusions that bad things are about to happen.”Rothschild and his colleagues then gathered each patient's hospital records from the time preceding their enrollment in the STOP-PD study to see what types of diagnoses he or she had received in the hospital emergency room or hospital psychiatric unit. The 65 inpatients had received, altogether, 130 diagnoses, meaning that some had received several diagnoses. Finally Rothschild and his team looked to see whether these 130 diagnoses had been made correctly.Over one-fourth had not, the researchers found. The three most common misdiagnoses were major depressive disorder without psychotic features, depression not otherwise specified, and mood disorder not otherwise specified. Misdiagnoses made less often included delirium, anxiety disorder not otherwise specified, and alcohol dependence.The erroneous diagnoses were more common in emergency rooms than on inpatient psychiatric units, and as Rothschild and his colleagues pointed out,“ It is quite striking that none of the patients with missed diagnoses were considered to have a psychotic disorder. This finding suggests that the physicians are missing the psychosis rather than the mood disorder. In many cases, it may be that the physician does not miss the symptom (for example, guilt, poverty, persecution), but does not recognize that the symptom is a delusion. In particular, the distinction between delusional and nondelusional guilt is frequently difficult.”These findings have important clinical implications, the researchers believe, since major depression with psychotic features often entails considerable morbidity and mortality, and its treatment differs from that for major depression alone. According to the APA 2000 practice guideline on the disorder, either an antipsychotic with an antidepressant or electroconvulsive therapy should be used, they noted.“As the process for DSM-V is beginning,” they continued, “it will be important to revisit the issue of whether 'major depression with psychotic features' should be a separate illness in DSM-V, as was recommended (but rejected) for DSM-IV, rather than a specifier of 'major depressive disorder,' a position where it can more easily be overlooked. The hope would be that if 'major depression with psychotic features' were a separate illness in DSM-V, it would result in greater awareness and more accurate diagnosis among practitioners.”Meanwhile, Rothschild offered the following tips on how psychiatrists can better detect psychotic depression:Develop a therapeutic relationship with patients so that they feel comfortable confiding their thoughts to you.Since patients are often guarded, use nonthreatening terms such as“ irrational worries” instead of “paranoia” or“ psychosis.”Listen carefully for clues of psychosis—for example, a patient saying something such as “My thoughts are not quite right.”Involve family members in the assessment process of the patient. They may have observed strange behavior or speech that might indicate psychosis.Also, Rothschild has written a book, Clinical Manual for the Diagnosis and Treatment of Psychotic Depression, to help physicians better diagnose the disorder. It will be available through American Psychiatric Publishing Inc. in November.The study was funded by the National Institute of Mental Health.An abstract of “Missed Diagnosis of Psychotic Depression at Four Academic Medical Centers” is posted at<www.psychiatrist.com/abstracts/200808/080813.htm>.▪ ISSUES NewArchived

Treatment of Psychotic Depression with Combination Olanzapine/Sertraline

Results from the National Institute of Mental Health's Study of the Pharmacotherapy of Psychotic Depression [STOP-PD] were presented at the American Psychiatric Association's 2008 Annual Meeting. To investigate the efficacy of a pharmacotherapeutic approach, STOP-PD looked at monotherapy with an antipsychotic versus an antipsychotic/antidepressant combination.

Serotonin Syndrome in Elderly Patients Treated for Psychotic Depression with Atypical Antipsychotics and Antidepressants: Two Case Reports

We report two cases of serotonin syndrome in elderly patients during treatment of psychotic depression with atypical antipsychotics and antidepressants. The first case is a 69-year-old man who was admitted for depression with psychosis and treated with trazodone, risperidone, and sertraline. Subsequently, he developed myoclonus, tremor, cogwheel rigidity, and diaphoresis. The second case is a 72-year-old female initially admitted to a medical inpatient unit for a change in mental status that presented as increased confusion, lethargy, slurred speech, and a fever of 101.5 degrees. She had been on phenelzine and quetiapine. In both cases, all symptoms resolved within 24 hours of the psychotropics being stopped. In both cases, we believe that serotonin syndrome was produced by a combination of an antidepressant and an atypical antipsychotic. There have been several case reports of serotonin syndrome from similar combinations of antidepressant and atypical antipsychotic treatment. Clinicians treating elderly patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome.

Risperidone in the treatment of psychotic depression

In the preset study, the authors investigated that effects of the antipsychotic drug risperidone on psychotic depression and examined the mechanism of risperidone to ameliorate psychotic depression. Fifteen patients met the DSM-IV criteria for major depressive disorder with psychotic features and the remaining five patients met those for bipolar I disorder (most recent episode depressed) with psychotic features (M/F: 8/12, age: 54 ± 18). All patients were evaluated regarding their clinical improvement using the Hamilton Rating Scale for Depression (Ham-D), and Positive and Negative Syndrome Scale (PANSS). In addition, plasma concentrations of HVA and MHPG were analyzed by HPLC. Patients with a 50% or more improvement in Ham-D score were defined as responders. Three were prescribed risperidone alone, and the other 17 were administered risperidone as an addition to preexisting antidepressants or mood stabilizers. The preexisting antidepressants or mood stabilizers were as follows: paroxetine (6), lithium (3), valproic acid (3), clomipramine (2), fluvoxamine (1), amitriptyline (1), amoxapine (1). The average dose of risperidone was 1.8 ± 0.5 mg/day. Eleven of twenty patients (55%) turned out to be responders 4 weeks after initiation of risperidone administration. No differences were observed between responders and nonresponders with respect to age, sex, Ham-D score before risperidone treatment, dose and plasma level of risperidone or its active metabolite, 9-hydroxyrisperidone. Plasma HVA levels before risperidone administration in responders were significantly higher than those in nonresponders. In addition, a significant correlation was observed between changes in plasma HVA level and the percentage improvement on Ham-D score. These results indicate that treatment with risperidone is effective to ameliorate psychotic depression, and the influence of risperidone on dopaminergic activity is associated with its efficacy.

Psychotic Major Depression

Numerous studies in the past three decades have characterised 'psychotic major depression', a subtype of major depression which is accompanied by delusions or other psychotic features. Evidence from phenomenological and neurobiological investigations indicates that this is a unique disorder with clinical and biological characteristics that are distinct from those of nonpsychotic depression and from other psychotic disorders. Treatment studies have provided evidence of small placebo effects and good responses to electroconvulsive therapy or combination treatment with an antidepressant plus an antipsychotic agent. However, until recently, there were only a few small, prospective, double-blind, controlled trials investigating the efficacy of antidepressant-antipsychotic combination pharmacotherapy, yet this constitutes the currently accepted and most universally applied 'standard of care' for psychotic depression. Treatment guidelines have been based largely on uncontrolled investigations of electroconvulsive therapy and studies using tricyclic antidepressants and first-generation antipsychotic drugs, which are not frequently chosen as first-line agents today because of concerns regarding tolerability and risks. However, recent open-label studies and large controlled trials of newer antidepressants and antipsychotics have yielded very divergent results thus far, so that the best treatment approach remains elusive. This review discusses the phenomenology and treatment of psychotic depression with a focus on the benefits and risks of various treatment approaches. Problems with this literature are highlighted, and strategies for future research are suggested.