Acute and transient psychotic disorders: A review of Indian research

ABSTRACT

Background:

Acute and transient psychotic disorder (ATPD) was recognized as separate from other psychotic disorders and described in the International Classification of Diseases (ICD) tenth revision for the first time. A lot of research on ATPD has been conducted in India over the last six decades, but a review focusing exclusively on Indian research on ATPD is not available.

Aim:

This paper aims to review the literature on ATPD emerging from India.

Methodology:

A combination of search terms “Acute and Transient Psychosis,” “acute psychosis,” “non-affective psychosis,” “non-affective psychotic disorder,” “reactive psychosis,” “first-episode psychosis,” and “India” were searched on various search engines like PUBMED, Medknow, Hinari, and Google Scholar. We also did a hand search for additional relevant articles, including published abstracts of the Indian Journal of Psychiatry from 2007 to 2023. Relevant papers were selected.

Results:

The prevalence of ATPD varies across different study settings, and it tends to have an abrupt to acute onset, and is primarily associated with stress. Few studies have assessed the subtypes of ATPD, and symptom profile has been inconsistently reported. There is a lack of trials on the effectiveness or efficacy of antipsychotics in ATPD patients. In a large proportion of patients initially diagnosed with ATPD, the diagnosis remains stable, with recurrence varying from 10% to 46.6% based on the duration of follow-up.

Conclusion:

There is a need for more multicentric studies, studies with larger sample sizes, and consistency in data about risk factors. There is a need to evaluate symptom profile, course, outcome, and treatment outcomes in patients with ATPD using validated instruments to improve our understanding. Further, there is a need for comparative studies to evaluate the risk factors for ATPD.

INTRODUCTION

Kraepelin[1] classified functional psychosis into dementia praecox (chronic course and gradual personality deterioration) and manic-depressive insanity (periodic course and complete interepisodic recovery). However, Kraepelin[2] also noted full recovery on follow-up in about 12.5% of his patients diagnosed with dementia praecox. However, he did not revise his conceptual view of functional psychotic disorders. Over the years, many investigators viewed schizophrenia as a heterogeneous group of disorders that share common psychotic symptoms with a variable course, response to medication, and outcome. In contrast, the affective disorder is seen as an episodic disorder with full interepisodic recovery and a relatively favorable outcome. However, there remained a group of non-organic or functional psychoses that failed to fit into the description of schizophrenia and affective disorder.

Many authors from Western countries during the late nineteenth century and the first seven decades of the twentieth century described an acute onset psychotic illness often preceded by stress, characterized by variable symptoms, with complete recovery and recurrence of episodes over time.[3,4,5,6,7,8,9,10] Different authors used terms like bouffee delirante,[4] “motility psychosis,”[11] confusional psychosis, “cycloid psychoses,”[12] schizophreniform psychosis,[8] reactive psychosis,[6] “psychogenic psychosis,”[7] and ‘hysterical psychosis’[10] to describe this kind of psychosis. Many authors from Asian and African countries also described “atypical psychosis,”[13] “acute primitive psychosis”, “acute paranoid psychosis,”[14] “transient psychosis,”[15] “catatonic-paranoid psychosis,”[16] and “acute psychotic reactions.”[17]

Thus, across the world, emerged the concept of a group of functional psychotic disorders that did not fall strictly into either the affective or schizophrenia categories. These disorders were characterized by acute onset, florid and variable symptomatology, and complete recovery. In some disorders, the presence of a stressor was not a must. Thus, these authors described the existence of a third psychosis with an acute onset, associated with stress, with changing symptomatology, and the subjects completely recovering from the same. Later systematic studies on acute functional psychoses led to the realization of the importance of classifying them under a separate heading in the classification systems.

International Classification of Diseases (ICD), sixth[18] and seventh[19] revisions (ICD-6 and ICD-7), included a category of acute schizophrenic reaction. In ICD-8,[20] the category of non-organic psychoses included psychotic conditions that were attributable to recent life experiences, including acute paranoid reaction (bouffee delirante) and unspecified categories of reactive psychoses. The ICD-9[21] replaced the term reactive psychosis with other and unspecified reactive psychoses, but the other categories were similar to ICD-8. The other and unspecified reactive psychoses listed psychogenic (reactive) psychosis as a subtype characterized by recovery within two weeks, the other subtypes being hysterical psychosis and psychogenic stupor. However, before ICD-10, “acute psychosis” was not included as a specified diagnostic entity. Different World Health Organization studies, such as the International pilot study of Schizophrenia (IPSS),[22] Determinants of Outcome of Severe Mental Health Disorders (DOSMed),[23] and Cross-cultural study of Acute Psychosis (CAP),[24] showed the existence of an acute onset psychotic illness that was different from schizophrenia and manic-depressive psychosis in terms of mostly having acute onset, onset associated with stress, and having a good outcome. These patients were considered to be having a non-affective, acute, remitting psychosis (NARP). This led to the recognition of acute psychosis as a separate entity and included acute psychosis in ICD-10. The ICD-10[25] described the category of acute and transient psychotic disorders (ATPD), with various subtypes that were later dropped in the ICD-11.[26]

The Diagnostic and Statistical Manual (DSM) in its second revision[27] included acute schizophrenic episode (characterized by the presence of schizophrenia symptoms along with confusion, emotional turmoil, excitement, and depression) and mentioned brief reactive psychosis but did not provide distinct diagnostic criteria. The category of brief reactive psychosis included various subtypes, i.e., psychotic depressive reaction, reactive excitation, reactive confusion, acute paranoid reaction, and reactive psychosis (unspecified). In DSM-III,[28] acute schizophrenic episode was replaced with schizophreniform disorder, characterized by the presence of schizophrenia symptoms, but the duration of symptoms was restricted to a maximum of six months. A brief psychotic disorder was retained but with specifications of sudden onset, duration of less than two weeks, and presence of a precipitating factor. The DSM-IIIR[29] changed the term brief psychotic disorder to brief reactive psychosis with changes in the duration criteria (up to one month) and adjustment of stressor criteria, allowing clinicians to classify different stressor events. DSM-IIIR[29] also used the term “provisional” for schizophreniform psychosis so that the diagnosis could be made before waiting for six months. The specification of with/without good prognostic features was also added. However, the DSM-III[28] and IIIR[29] diagnostic criteria were criticized because it was challenging to differentiate schizophreniform disorder of less than one month’s duration from brief reactive psychosis, and the concept of brief reactive disorder seemed to have been altered, and the criteria were made too restrictive, limiting the clinician’s ability to study an appropriate cohort of patients. To overcome some of these limitations, in DSM-IV,[30] schizophreniform psychosis was defined by the presence of active symptoms for one month, to appear after the first noticeable change in behavior/functioning to differentiate it from brief psychotic disorder. In DSM-IV,[30] the category of brief psychotic disorder replaced that of brief reactive psychosis. The duration of brief psychotic disorder ranged from one day to one month. The specifiers used for the group were those with/without marked stressors and with postpartum onset (within four weeks postpartum). DSM-5[31] also lists brief psychotic disorder as mentioned in DSM-IV with the same specifiers.

Much research on ATPD has been conducted in India over the last six decades. Although many reviews have attempted to collate information on ATPD, none have focused explicitly on Indian literature only. This review attempts to evaluate the Indian research on ATPD.

METHODOLOGY

For this review, a combination of search terms “Acute and Transient Psychosis,” “acute psychosis,” “non-affective psychosis,” “non-affective psychotic disorder,” “reactive psychosis,” “first-episode psychosis,” and “India” was searched on various search engines like PUBMED, Medknow, Hinari, and Google Scholar. All published literature was included irrespective of the time of publication. Apart from this, a hand search was carried out, and any relevant additional articles were included. SK performed the search, and any discrepancy was addressed by SG. Additionally, all the available abstracts as part of the Supplement of the Indian Journal of Psychiatry from 2007 to 2023 were reviewed for information on acute psychosis, first-episode psychosis, or acute and transient psychosis. We included studies on first-episode psychosis, as many of these studies had a varying proportion of patients with ATPD.

Selection of studies

Only articles published in the English language that originated (having at least one author from India) or contained data from India on “acute and transient psychosis,” “non-affective psychosis,” “non-affective psychotic disorder,” “reactive psychosis” or “first-episode psychosis” (FEP) were included. Articles on “postpartum psychosis” (PPP) or “acute psychosis” were also considered for inclusion if they contained relevant information. These included original articles, review articles, case reports, and case series. Data published as conference abstracts or theses were also included if these were accessible.

Additional searches were done for the relevant articles that did not have “acute psychosis” or ATPD as keywords but included information on the prevalence of ATPD. We will use the term ATPD to describe all these conditions in this article for description purposes.

Data extraction and management

SG generated the data extraction form. It included data related to the identification of the study, epidemiology, clinical features, etiology or risk factors, treatment, course, and outcome. SK did data extraction. SG checked the fidelity of the extraction.

The initial search yielded 37 articles, and 67 more publications were obtained from further hand searches. Of these 104 articles, two were excluded as the data were not from India. A search for conference abstracts published in the Indian Journal of Psychiatry yielded 139 abstracts, out of which results were not available for 18, and these were excluded.

Hence, 102 articles and 121 abstracts were included in the final review. An attempt was also made to pool the data whenever feasible to improve the understanding of the data. Four additional articles were included that reflected the prevalence of ATPD in different settings.

We attempted to pool the data from different studies for some of the factors. While pooling the data, we weighed for the sample size of different studies.

RESULTS

Of these 223 articles, there were 61 original articles, 32 case reports, eight review articles, one thesis, and 121 conference abstracts.

Studies focusing on the validation of ATPD

Classification

Malhotra et al.[32] tried to classify the patients with acute onset psychosis using ICD-9 and Catego criteria and reported that 40% of subjects did not fit into either manic-depressive psychosis or schizophrenia. When an attempt was made to classify the patients diagnosed as non-organic acute psychosis, they found support for the existence of acute and transient psychosis as separate entities. This study further revealed that patients with acute psychoses had a higher stress frequency than those in schizophrenia and manic-depressive psychosis patients and had undifferentiated symptomatology akin to the description of acute polymorphic psychoses at presentation. An Indian Council of Medical Research (ICMR) multicentric collaborative study of 1985[33] also reported a similar profile of acute psychosis, i.e. 50% of patients with acute onset psychosis didn’t fit into schizophrenia, manic-depressive psychosis, or depression when Catego criteria were used and 40% of the patients had non-organic psychosis as per the ICD-9 criteria. It also reported that the core cases of acute psychosis had less anxiety, less expansive mood, and less perplexity than other entities.

Duration of ATPD

Susser et al.[34] demonstrated that the duration of psychotic illness episodes in non-affective acute psychoses has a bimodal distribution pattern, with a point of rarity between two symptom score clusters. In 80% of the cases, the duration was less than 28 weeks, and in the rest of the 20% of cases, it was more than a year. Although treatment response could be a potential confounder in the study, the findings never-the-less suggested the probability of two different diagnostic entities, one with a better and the other with a poorer prognosis. A reanalysis of the DOSMeD study, which included patients from India too, showed that acute psychosis has a modal duration of 2–4 months longer than that permitted by the ICD-10 criteria of ATPD. Further, it was shown that these duration criteria were the critical determining factor in patients being classified with ATPD or not. Based on these findings, authors suggested the need to relook at the duration criteria for ATPD.[35]

Studies focusing on epidemiology

Sixty-two original articles provided some or other epidemiological information on patients of ATPD. Some of these have focused explicitly on ATPD only, whereas others have reported patients with ATPD forming a small subgroup of the whole study sample.

Incidence

Susser and Wanderling,[36] in their study on NARP, found that the incidence of NARP was about 10-fold in the developing country setting compared to the industrialized country setting for both sexes. Also, the annual incidence of NARP per 10,000 people in men was about half that in women. No other study from India has evaluated the incidence of ATPD.

Prevalence

None of the community-based studies have reported the prevalence of ATPD in the community samples. The ICMR study[33] conducted about four decades back at four centers (Patiala, Bikaner, Goa, and Bikaner), which included 323 patients with acute psychosis, suggested that in the Indian context, 8.7% of all patients with psychosis presenting for the first time are likely to be suffering from acute psychosis. The report proposed that acute psychosis consists of three groups—clinical schizophrenia (35%), manic-depressive psychosis (25%), and the remaining 40% who do not belong to a specific category.

In the later studies, there is a lack of studies explicitly focusing on the prevalence of ATPD in outpatient, inpatient, and emergency settings. However, studies focusing on different populations have reported the prevalence of ATPD.[37 38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57] One of the studies from Chandigarh that focused on the first prescription of patients presenting to the outpatient setting of a tertiary care hospital suggests the prevalence of ATPD to be 2.26% in new adult patients presenting to the walk-in clinic.[37] The prevalence of ATPD in older people from the same dataset was reported to be 0.6%.[38] One of the studies from Ranchi that selected patients of affective and non-affective psychosis reported the prevalence of ATPD to be 1.7%.[39] Studies that have specifically evaluated the prevalence among inpatients have reported the prevalence of ATPD to be 3.2%.[57] However, studies focusing on specialized inpatient groups have said the prevalence to be 1.3% in those with dermatological comorbidities.[40] In the emergency setting, a prevalence of 2.3% has been reported among patients referred to the psychiatry emergency team.[41] Studies focusing on patients with FEP have estimated the prevalence of ATPD to be 5.6% among those with FEP inpatients,[42] 14%[43] in a mixed inpatient/outpatient setting, 26.5% in the outpatient setting,[44] and 42.4%[45] among outpatients with substance use disorders. Among the special populations in the inpatient setting, the prevalence of ATPD has been reported to be 25.6% in females with postpartum psychosis (PPP),[46] 39% among PPP females (with 55% of PPP women with catatonia having ATPD and 35% of PPP women without catatonia having ATPD),[47] and 40% in postpartum females admitted in the mother–baby unit.[48] Among adolescent patients attending the outpatient services, the prevalence was found to be 1.62%,[49] and the prevalence in patients presenting with late-onset psychosis to be 16.6%.[50] Among adolescent patients receiving ECT, the prevalence of ATPD has been estimated to be 8%,[51] whereas among adult patients receiving ECT, it has been estimated to be 14.9%.[52] A study that evaluated prevalence in patients with COVID-19 reported the prevalence of acute psychosis to be 0.14%.[53] In a mixed setting of both inpatient and outpatient populations of females with postpartum depression (PPD)/PPP, the prevalence of ATPD ranged from 7.7%[54] to 61%.[55] A study that evaluated patients with suspected autoimmune encephalitis reported the prevalence to be 53.4%[56] [Table 1].

Table 1.

Prevalence of ATPD across different treatment settings

Study	Setting	Population	Type	Site	Sampling	Total sample	ATPD sample	Prevalence of ATPD
Grover et al., 2012[37]	Outpatient Walk-in Clinic	Adults	Tertiary GHPU	Chandigarh	Consecutive	10214	231	2.26%
Chand et al., 2014[45]	Outpatient FEP	Adults	Tertiary	Bangalore	Not mentioned	139	59	42.4%
Jilani et al., 2017[44]	Outpatient FEP	Adults	Tertiary GHPU	Lucknow	Not mentioned	151	40	26.5%
Kumari et al., 2013[39]	Outpatient- affective and non-affective psychosis	Adults	Tertiary	Ranchi	Purposive	60	1	1.7%
Grover et al., 2012[38]	Outpatient- all Elderly Walk-in	Elderly	Tertiary GHPU	Chandigarh	Consecutive	1192	7	0.6%
Grover et al., 2016[57]	Inpatient- all inpatients	Adults	Tertiary GHPU	Chandigarh	Consecutive	496	16	3.2%
Kumar et al., 2013[40]	Inpatient- with pemphigus or psoriasis	Adults	Tertiary GHPU	Chandigarh	Non-consecutive	80	1	1.3%
Sadath et al., 2018[42]	Inpatient- FEP	Adults	Tertiary	Bangalore	Convenience	71	4	5.6%
Grover et al., 2021[41]	Emergency Consultation-Liaison Services	Adults	Tertiary GHPU	Chandigarh	Consecutive	5563	128	2.3%
Babu et al., 2013[46]	Inpatient- female patients with PPP	Postpartum	Tertiary	Bangalore	Consecutive	78	20	25.6%
Nahar et al., 2016[47]	Inpatient -female patients with PPP with or without catatonia	Postpartum	Tertiary	Bangalore	Retrospective chart review	200	78	39%
Dutta et al., 2021[53]	COVID-19 inpatients	COVID-19 patients	Tertiary GHPU	Delhi	Not mentioned	6198	9	0.14%
Banyal et al., 2018[58]	FEP drug naïve patients- either inpatient/outpatient	Adults	Tertiary GHPU	Jammu	Not mentioned	79	14	17.72%
Prakash et al., 2021[43]	FEP- either inpatient/outpatient	Adults	Tertiary GHPU	Armed forces hospitals	Consecutive	100	14	14%
Grover et al., 2018[54]	Females with PPD/PPP- either inpatient/outpatient	Postpartum	Tertiary GHPU	Chandigarh	Consecutive	18	1	7.7%
Thippeswamy et al., 2015[55]	Females with PPP- either inpatient/outpatient	Postpartum	Tertiary	Bangalore	Consecutive	123	75	61%
Manohar et al., 2017[52]	Patients receiving ECT- either inpatient/outpatient	Adults, ECT sample	Tertiary GHPU	Pondicherry	Not mentioned	148	22	14.9%
Grover et al., 2013[51]	Adolescent patients receiving ECT- either inpatient/outpatient	Adolescent, ECT sample	Tertiary GHPU	Chandigarh	Consecutive	25	2	8%
Bharadwaj et al., 2019[56]	Acute psychosis patients suspected to have autoimmune encephalitis	Adults	Tertiary GHPU	Pondicherry	Not mentioned	15	8	53.4%
Patra and Panda, 2023[59] $	Inpatient- 12-month prevalence	Adults	Tertiary GHPU	Mumbai	Not mentioned	-	-	9.4%
Yadawad et al., 2018[48] $	Inpatient- mother–baby unit	Postpartum	Tertiary	Bangalore	Purposive	43	17	40%
Mukherjee et al., 2015[49] $	Outpatient	Adults	Tertiary	Tezpur	Not mentioned	-	-	6.3%
Lukose et al., 2014[60] $	Adolescent patients- either inpatient or outpatient	Adolescent	Tertiary GHPU	Vellore	Not mentioned	5054	82	1.62%
Sushma, et al. 2010[50] $	Late-onset psychosis- either inpatient or outpatient	Elderly	Tertiary	Bangalore	Not mentioned	40	7	16.6%

ATPD: Acute and transient psychotic disorder; PPP: Postpartum psychosis; PPD: Postpartum depression; GHPU: General Hospital Psychiatric Unit, FEP: First-episode psychosis; ECT: Electroconvulsive therapy. ^$data from the published conference abstract

Sociodemographic profile

There is a lack of consistency across different studies with respect to some of the demographic variables. Although the initial studies[32,33,61] reported female preponderance and a higher proportion of them belonging to rural locality,[32] in the recent studies, the percentage of males across different studies involving the adult populations of both the sex have varied from 28.9%[62] to 100%,[53,63] and the percentage of the married people in different studies has ranged from 11.8%[64] to 91.6%.[53] Similarly, across different studies, 8.1%[65]–96.7%[66] of patients with ATPD belonged to the rural locality, 30%[67]–88%[68] belonged to nuclear family setup, 50%[69]–100%[70] were Hindu by religion, 8.3%[53]–83.3%[71] were unemployed, and 8%[72]–89%[73] of the subjects in various studies belonged to lower socioeconomic status. The mean age in years of the study participants across different studies has ranged from 21.3[63] to 37.67,[53] and the mean years of education ranged from 7.11[74] to 13.95[75] years.

Three studies that evaluated ATPD among the adolescent population (<18 years)[51,60,76] reported the proportion of male subjects to range from 44%[60] to 64%,[51] with a mean age of 14[76] to 15.7.[60] One study on late onset psychosis[50] reported mean age of 71.6 years and 52.8% being of the male gender.

Six studies that have focused on postpartum population[46,47,48,54,55,77] with sample sizes of ATPD in the whole study sample ranging from 1[54] to 78[47] reported the mean age ranging from 22.9[46] to 27.4[48] years, mean years of education ranging from 7.5[46] to 11.5[54] years, 7.7%[54] of patients being employed, 31.7%[55] to 92.3%[54] belonging to middle socioeconomic status, 19.2%[46] to 60.5%[48] belonging to rural locality and 46.2%[54] to 77.2%[55] being Hindu by religion. In one study, the authors reported that 21.1% of patients with ATPD were migrant population.[78]

The pooled analysis of data (the studies focusing on adolescent, geriatric, and postpartum were not included) from the available studies suggests that the male subjects form 51.38% (SD: 16.25) of the study sample, 57.48% (SD: 22.48) of the subjects are married, and 46.36% (SD: 22.59) unemployed and additional one-fourth (23.08%) are homemakers. More than half of the subjects with ATPD belong to lower socioeconomic status (mean: 53.49%; SD: 20.60), rural locality (mean: 60.85%; SD: 21.22), and nuclear family setup (mean: 57.26%; SD: 18.74). Over three-fourths of the sample belonged to the Hindu religion (mean: 80.43%; SD: 15.03) [Table 2].

Table 2.

Sociodemographic profile of ATPD

Variable	Pooled data as mean (SD)	Range in %	References
Gender	Male: 51.38 (16.25) Female: 48.62 (16.25)	28.9[62]-100[53,63] 0[53,63]-71.1[62]	[32,34,36,39,40,42,44,45,49,52,53,56,58,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101]
Marital status	57.48 (22.48)	11.8[64]-91.6[53]	[39,40,42,44,53,56,58,64,66,67,70,71,72,73,74,78,79,80,81,84,85,86,91,99,100,101]
Occupation	Unemployed: 46.36 (22.59) Housewife: 23.08 (16.38)	8.3[53]-83.3[71] 5.6[42]-50[101]	[39,42,53,56,58,64,66,70,71,72,73,75,79,86,99,100] [42,56,64,65,66,78,99,100,101]
Socioeconomic status	Low: 53.49 (20.60) Middle: 41.46 (23.17) High: 18.29 (21.08)	8[72]-89[73] 10[73]-80[96] 1[73]-60[71]	[39,44,56,61,64,66,68,70,72,73,74,78,79,86,92,96,99,100] [39,44,56,61,66,70,72,73,74,79,92,96,99] [44,61,71,72,73,99]
Locality	Rural: 60.85 (21.22)	8.1[65]-96.7[66]	[34,39,40,44,56,61,65,66,67,69,70,71,72,73,74,75,78,79,81,83,84,86,90,93,95,96,99,100]
Family setup	Nuclear: 57.26 (18.74)	30[67]-88[68]	[44,58,62,66,67,68,69,70,71,72,73,75,79,80,86]
Religion	Hindu: 80.43 (15.03)	50[69]-100[70]	[39,40,42,44,68,70,71,72,73,78,80,85,100]

Studies focusing on clinical profile

Overview

Most of the studies that have evaluated patients with ATPD have provided information on some or other clinical aspects of ATPD[49,62,63,66,67,70,72,73,74,75,76,78,79,84,88,89,90,91,92,97,98,99,100,101,102,103,104,105] exclusively. At the same time, some studies that have provided information about the clinical profile of ATPD also included patients with other acute psychotic states[32,34,35,36,39,40,51,52,53,56,61,65,69,80,82,83,85,93,94,95,96,106] like first episode psychosis,[42,43,44,45,58,64,71,86,107,108] postpartum psychosis,[46,47,54,55,109] etc. The sample size of ATPD in these studies ranged from 1[39,40,54] to 298.[49]

Nosology and assessment tools

Studies before 2000 preferred ICD-9[32,33,34,35,36,61,65,81,82,83,85,93,95,96] or DSM-III[69,80] criteria to diagnose acute psychosis, but all later studies have relied on the ICD-10 criteria of ATPD.

Varied assessment tools have been utilized to either diagnose, rate the severity of the psychosis, or evaluate the symptom profile. The commonly used scales include Brief Psychiatric Rating Scale (BPRS),[39,42,43,56,63,70,72,74,75,76,79,88,98,99,102,105] Present State Examination (PSE),[32,34,35,36,85,93,95,96] Positive and Negative Syndrome Scale (PANSS),[39,43,44,45,64,66,71,78,86] and Comprehensive Psychopathological Rating Scale (CPRS).[40,46,62,69,78,80,92]

Onset

In the ICMR multicentric study,[33] in 54% of the patients, the time from the first symptom to the full-blown psychosis was less than 48 hours, in 33% of patients this was between 48 hours and 1 week, and in only 1% of patients, this period was between 1 and 2 weeks. Later, other studies have also reported the nature of the onset of the ATPD.[39,46,51,53,54,62,66,67,70,78,79,85,91,101] Among these studies, episodes were of abrupt onset in 13%[78] to 75%[53] of the study samples, acute in 25%[53] to 87.5% of the samples,[78] subacute in 6.7%[79] to 16.2% of the samples,[85] and insidious in 15.4%[54] to 61.7%.[39] A study that compared the onset of patients with ATPD and mania reported a significant majority of patients with ATPD had an abrupt onset of illness when compared to patients with mania.[110]

Studies focusing on risk factors or etiology

Studies that have assessed risk factors for ATPD have identified risk factors like life events or stressors,[53,61,66,67,73,74,78,79,82,83,84,85,88,89,101] immune markers,[75,88] cortisol,[88] and anti-NMDA antibodies to be associated with ATPD[56] [Table 3].

Table 3.

Factors associated with the onset of ATPD/acute psychosis

Genetic	History of ATPD in first-degree relatives[111]
Psychosocial stressors	Common: Child sexual abuse,[112] unemployment in self or family member,[66] failure in examination or interview,[66,84] anticipated financial loss,[84] accident of family member,[84] threat to life or death of family member,[84] migration,[113] earthquake[114] Women: return to or departure from the family of origin,[82] death or illness of family member,[67] marriage or engagement,[67] violence,[67] childbirth,[61] abortion of male fetus,[84] puerperium[84] Men: job distress,[82] marital and family conflicts,[67] financial or occupational problem[67] COVID-19 associated: diagnosis in relative[53]
Physiological or biological factors	Fever,[61,67,73,82,83,88] chikungunya fever,[115] summer peak[61,73,105]
Personality features/traits	Low neuroticism,[89] high conscientiousness,[89] suspiciousness,[80] cyclothymic traits,[80] hysterical personality,[33] schizoid personality,[33] high sensitivity,[87] immaturity,[87] lack of confidence,[87] poor scholastic performance,[116] lying,[116] excessive anxiety,[116] shyness,[116] evolving borderline personality[117]
Immune/blood markers	Cortisol,[88] immune markers like Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-17, tumor necrotic factor (TNF)- alpha and tumor growth factor (TGF)-beta,[75,88] thyroid-stimulating hormone,[118] testosterone,[119] cholesterol,[120] dehydroepiandrosterone sulfate (DHEA-S)/cortisol ratio,[121] DHEA-S,[122] brain-derived neurotrophic factor,[123] N-Acetyl aspartate,[124] insulin resistance,[125] serum bilirubin,[126] free T4,[127,128] monocyte count,[129] eosinophil count,[129] monocyte lymphocyte ratio,[129] neutrophil-to-lymphocyte ratio[130]
Organic factors	Anti-NMDAR encephalitis,[131,132,133,134,135,136,137,138,139,140,141,142,143] quadrigeminal cistern lipoma,[144] porencephalic cyst,[145] acute disseminated encephalomyelitis,[146] Moyamoya disease,[147,148] retinitis pigmentosa,[149] acute cutaneous lupus erythematosus,[150] systemic lupus erythematosus,[151] primary Sjogren’s syndrome,[152] complex partial seizure,[153] post-ictal phase,[154] COVID-19 infection,[155] viral encephalitis,[156] subacute sclerosing panencephalitis,[157] disseminated neurocysticercosis,[158] Scrub typhus,[159] severe hypothyroidism,[160] hyperthyroidism,[161] Hashimoto’s thyroiditis,[162] hypoglycemia,[163] panhypopituitarism,[164] Cushing’s syndrome,[165] leukodystrophy,[166] cerebral venous sinus thrombosis,[167] thalamic infarct,[168] Stickler syndrome,[169] Sturge–Weber syndrome,[170] Mayer–Rokitansky–Kuster–Hauser syndrome,[171] Immunoglobulin G4 (IgG4) related disease,[172] Fahr’s syndrome with pseudopseudohypoparathyroidism,[173] Wilson’s disease[174]
Drugs	Iohexol,[175] phenytoin,[176,177] levetiracetam,[178] disulfiram,[179,180,181] combination of baclofen and disulfiram,[182] armodafinil,[183] ciprofloxacin,[184] bupropion,[185] mephentermine,[186] antitubercular drugs[187] like cycloserine,[188,189] ethambutol,[190] combination of interferon alpha2B and ribavarin,[191] dapsone[192]
Others	Meditation (concentrative or transcendental type),[193] COVID-19 vaccine[194]

Family studies

Das et al.[111] studied 40 probands of ATPD and schizophrenia each and found that first-degree relatives of ATPD probands had a higher prevalence of ATPD than probands of schizophrenia. This study also found that ATPD as a group had a differential pattern of risk of illness compared to schizophrenia.

Stressors

Stressors have been assessed using the Presumptive Stressful life event scale (PSLES)[66,67,69,74,78,79,80,84,89,98,195,196] in most studies or as a part of routine history taking. While some studies[73,78,79] found no association between the onset of psychosis with stressors, other studies found a significant association between the two.[61,66,67,74,80,82,195,196] However, it is important to note that many of these studies have not included a control group. Some studies have noted that the nature of stress differed between males and females.[61,67,82] Common psychosocial stressors that have been reported to be associated with the onset of ATPD include unemployment in self or family member,[66] failure in examination or interview,[66,84] anticipated financial loss,[84] accident of family member,[84] the threat to life or death of family member,[84] migration,[113] and earthquake.[114] Those specific to the female gender are return to or departure from the family of origin,[82] death or illness of family member,[67] marriage or engagement,[67] violence,[67] childbirth,[61] abortion of male fetus,[84] and puerperium.[84] In males, job distress,[82] marital and family conflicts,[67] and financial or occupational problems[67] were reported as risk factors.

One study reported that patients with a preceding stressor were more likely to develop three or more episodes of ATPD in the long term.[101] The stress-vulnerability hypothesis in the etiology of ATPD was proven by Das et al.,[84] as patients with a family history reported a significantly lower number of life events and stress scores than those without a family history. News about COVID illness and diagnosis in colleagues were significant stressors reported in some of the recent studies.[53] Fever,[61,67,73,82,83,88] especially chikungunya fever[115] and summer peak[61,73,105] as specific stressors, have also been studied in earlier studies and are associated with the onset of psychosis.

Vulnerability factors: Personality

Regarding personality features, the ICMR study[33] reported that most (74%) patients have normal personalities. Regarding personality features, different studies have reported other personality traits such as low neuroticism and high conscientiousness,[89] suspiciousness and cyclothymic traits,[80] and hysterical or schizoid personality.[33] Kapur and Pandurangi[87] noted that subjects with reactive psychosis have a vulnerable personality with features of high sensitivity, immaturity, and lack of confidence.

Child sexual abuse as a stressor for ATPD and other psychiatric disorders was reported by a recent case series.[112] Some studies have reported an association of FEP with premorbid poor academic performance, lying, excessive anxiety, and shyness in those who developed childhood onset FEP.[116] Evolving borderline personality disorder was reported in an adolescent who developed ATPD.[117]

Immune or other blood markers

Some of the studies have evaluated the serum levels of cortisol[88] and immune markers like Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-17, Tumor Necrotic factor (TNF)- alpha, and Tumor Growth Factor (TGF)-beta as potential risk factors.[75,88] These studies suggest that patients with ATPD have elevated pro-[75,88] and anti-[88] inflammatory cytokine levels compared to healthy controls. Other blood markers that have been studied include thyroid-stimulating hormone,[118] testosterone,[119] cholesterol,[120] dehydroepiandrosterone sulfate (DHEA-S)/cortisol ratio,[121] DHEA-S levels,[122] brain-derived neurotrophic factor,[123] N-acetyl aspartate,[124] insulin resistance,[125] serum bilirubin[126] in FEP patients, and thyroid function[127,128] (free T4) in patients with PPP.

FEP was found to differ from multi-episode psychosis significantly concerning inflammatory markers like monocyte, eosinophil count, and monocyte-lymphocyte ratio.[129] A study reported a high neutrophil-to-lymphocyte ratio[130] in patients with ATPD, which also corroborated with disease severity.

Organic factors

Although several case reports have shown an association between anti-NMDAR encephalitis and ATPD,[131,132,133,134,135,136,137,138,139,140,141,142,143] a recent study, however, failed to detect anti-NMDA antibodies in patients with acute psychosis with one clinical feature suggestive of autoimmune etiology.[56] Other diseases that have been reported in case reports/series to be associated with the onset of acute psychosis include quadrigeminal cistern lipoma,[144] porencephalic cyst,[145] acute disseminated encephalomyelitis,[146] Moyamoya disease,[147,148] retinitis pigmentosa,[149] acute cutaneous lupus erythematosus,[150] systemic lupus erythematosus,[151] primary Sjogren’s syndrome,[152] complex partial seizure,[153] post-ictal phase,[154] COVID-19 infection,[155] viral encephalitis,[156] subacute sclerosing panencephalitis,[157] disseminated neurocysticercosis,[158] Scrub typhus,[159] severe hypothyroidism,[160] hyperthyroidism,[161] Hashimoto’s thyroiditis,[162] hypoglycemia,[163] panhypopituitarism,[164] Cushing’s syndrome,[165] leukodystrophy,[166] cerebral venous sinus thrombosis,[167] thalamic infarct,[168] Stickler syndrome,[169] Sturge–Weber syndrome,[170] Mayer–Rokitansky–Kuster–Hauser syndrome,[171] immunoglobulin G4 (IgG4)-related disease,[172] Fahr’s syndrome with pseudopseudohypoparathyroidism,[173] and Wilson’s disease.[174]

Other factors that are associated with the onset of acute psychosis in various case reports include the concentrative or transcendental type of meditation,[193] COVID-19 vaccine,[194] drugs like iohexol,[175] phenytoin,[176,177] levetiracetam,[178] disulfiram,[179,180,181] a combination of baclofen and disulfiram,[182] armodafinil,[183] ciprofloxacin,[184] bupropion,[185] mephentermine,[186] antitubercular drugs[187] like cycloserine,[188,189] ethambutol,[190] a combination of interferon alpha2B and ribavarin,[191] and dapsone.[192]

Family history

Some studies have evaluated a family history of any mental illness[39,44,46,49,54,58,64,66,71,73,75,76,78,79,84,85,90,96,97] and specifically any psychotic illness[43,56,62,72,79,90,99,101,102] including ATPD[75,76,84] to be associated with the development of ATPD. Das et al.[84] reported that family history-positive patients were comparable to family history-negative patients on several sociodemographic and clinical parameters. Screening for Schizotypy in 30 unaffected adolescent siblings of FEP found 57% of them at high risk of psychosis, with females having a higher degree of referential and magical thinking, paranoid ideation, odd behavior, and social anxiety.[197]

Neurological soft signs (NSS)

In drug naïve patients with FEP, NSS were found to be more prevalent than in those with medical illness, with at least one NSS in 81.3%, also correlating with severity of psychosis, duration of illness, and PANSS score.[198,199]

Diagnostic subtypes

Only 16 studies[35,49,60,72,76,78,79,84,91,92,93,98,99,100,101,102] have provided subtypes of ATPD as per the ICD-10, and the prevalence of acute polymorphic psychotic disorder without symptoms of schizophrenia across different studies ranges from 3.3%[99] to 72%[99] with 5 out of 14 studies estimating the same to be more than 40%. The prevalence of acute polymorphic psychotic disorder with symptoms of schizophrenia ranges from 10%[84] to 54.4%,[78] and that of acute schizophrenia-like psychotic disorder ranges from 2.4%[60] to 60%[35] across the different studies [Table 4].

Table 4.

Subtype of ATPD in different studies

Study	ATP sample	F23.0	F23.1	F23.2	F23.3	F23.8	F23.9
Agarwal & Sitholey, 2006[76]	23	47.8%	13.1%	13.1%	4.3%	21.7%	-
Brar et al., 2022[79]	60	21.7%	53.3%	20%	5%	-	-
Chandak & Gowda, 2017[78]	57	22.8%	54.4%	10.5%	1.8%	10.5%	-
Chaudhuri et al., 2000[99]	30	3.3%	-	60%	-	36.7%	-
Das et al., 2001[84]	40	52.5%	10%	7.5%	10%	7.5%	12.5%
Kar & Dhanasekaran, 2017[100]	140	15.7%	2.15%	12.85%	-	69.3%	-
Khanna et al., 1997[102]	40	2.5%	-	55%	-	42.5%	-
Mojtabai et al., 2000[35]	20	-	-	7%	-	4%	-
Rajkumar, 2015[101]	20	10%*		30%	20%	40%
Rajkumar, 2016[91]	46	16%*		30%*
Sahoo et al., 2016[72]	25	72%	28%	-	-	-	-
Sajith et al., 1999[92]	80	43.8%	-	8.8%	20%	27.5%	-
Susser et al., 1998[93]	17	-	-	12%	-	-	-
Acharya et al., 2013[98] $	30	33.3%	-	-	-	-	40%
Lukose et al., 2014[60] $	82	57.3%	19.5%	2.4%	-	-	20.7%
Mukherjee et al., 2015[49] $	298	32.2%*		26.8%	-	-	-
The pooled prevalence of subtypes	1008	25.11%	13.10%	17.09%	4.29%	16.70%	0.05%

F23.0: Acute polymorphic psychotic disorder without symptoms of schizophrenia; F23.1: Acute polymorphic psychotic disorder with symptoms of schizophrenia; F23.2: acute schizophrenia-like psychotic disorder; F23.3: other acute predominantly delusional psychotic disorders; F23.8: other ATPD; F23.9: Unspecified ATPD. *common prevalence was equally divided between the subtypes for calculation of pooled prevalence; ^$data from published conference abstracts

When an attempt was made to evaluate the prevalence of various subtypes of ATPD across different studies, ATPD without symptoms of schizophrenia form 25.11%, followed by acute schizophrenia-like psychotic disorder (17.09%), other ATPD (16.70%), an acute polymorphic psychotic disorder with symptoms of schizophrenia (13.10%), other acute predominantly delusional psychotic disorders (4.29%), and unspecified ATPD (0.05%) [Table 4].

Symptoms

Symptom profile has been reported inconsistently across various studies. Some studies have specifically reported the prevalence of specific psychotic symptoms, the commonest being delusions,[53,66,80,96,98] followed by hallucinations[53,66,80,96,98] and Schneider First Rank Symptoms (SFRS).[53,101] Mishra et al., [97] also report delusion as the most typical symptom, followed by abnormal speech, hallucinations, and disorganized behavior.

Kanwal et al., 2013[109] studied patients with PPP and reported that 18% had psychotic symptoms without affective symptoms, 24% had a mixture of both, and 46% had only affective symptoms. Another study on 50 patients of PPP[77] showed 51% had a BPRS score of 24. The severity of symptoms on BPRS was studied by Kumar et al., 2013[105] in 50 patients of ATPD, which showed suspiciousness, hallucinations, unusual thought content, and uncooperativeness to be moderately severe, while anxiety and grandiosity were moderate. There are also reports of typical[200,201,202] and atypical presentations like Folie a deux,[203] Folie a trois,[204] olfactory hallucination[205] in late-onset ATPD, and somatic delusion[206] like Koro in patients of ATPD.

Other studies have also reported the prevalence of formal thought disorder,[91] emotional changes including withdrawal,[78] lack of emotions[78] or emotional lability,[78,91] violence,[86,101] hostility,[80] irritability,[34,91] psychomotor agitation[96,98] or retardation,[54,78] catatonia,[46,47,91] mood changes like elation[54,78,80,96] or sadness,[54,66,78,80,91,96] worries,[80] obsessive-compulsive symptoms,[54] and anxiety.[53,66]

Some studies on suicidality report suicidal behavior,[46,54,78,101,103] including attempt,[91,103] and infanticidality.[46] Phutane et al., 2014[108] found a statistical correlation between prior hospitalization at baseline and suicidal ideation, plan, and attempt. Case reports on various means of self-harm in ATPD include bilateral enucleation,[207] ingestion of tooth brush,[208] and head banging.[203]

Other studies report symptoms like poor attention[66] or concentration,[78,80] lack of judgment[66] or insight,[66] confusion or perplexity,[53,91,96] altered biofunctions[54] like sleep disturbance,[53,62,80] appetite disturbance,[62,80] and autonomic disturbance[80] [Table 5]. Wide variation in prevalence could be attributed to using different assessment tools and different study populations like ATPD, FEP, and PPP. The ICMR study[33] reported that most patients with acute psychosis have paranoid features. Malhotra et al.[32] studied all cases of acute onset psychosis and noted that acute non-organic psychosis presents with a wide variety of symptoms. An attempt to classify all patients with acute psychosis using statistical methods showed that there are six symptom clusters, i.e. manic-depressive psychosis, confusional psychosis, schizophrenic psychosis, reactive hysteriform psychosis, reactive undifferentiated psychosis, and hallucinatory psychosis.[32]

Table 5.

Pooled data on symptom profile of ATPD

Symptom	Prevalence	References
Any delusions	40%[96] to 98%[66]	[53,66,80,96,98]
Delusion of persecution	47.8%[91] to 86%[78]	[62,78,80,91]
Delusion of reference	15.2%[91]	[91]
Delusion of grandiosity	5%[80] to 10.8%[91]	[80,91]
Somatic delusions	2.2%[91]	[91]
Other delusions	13%[91] to 36.8%[78]	[78,80,91]
Any hallucinations	30%[96] to 95%[66]	[53,66,80,96,98]
Auditory hallucinations	36%[80] to 36.9%[91]	[80,91]
Commenting AH	35.1%[78]	[78]
3rd person AH	30%[39]	[39]
Other AH	75.4%[78] to 91.1%[62]	[62,78]
Visual hallucinations	22%[80]	[80]
Other hallucinations	5%[80]	[80]
Hallucinatory behavior	77.2%[78]	[78]
SFRS present	25%[53] to 30%[101]	[53,101]
Formal thought disorder	30.4%[91]	[91]
Unusual thought content	57%[66]	[66]
Pressure of speech	31.6%[78]	[78]
Withdrawal	42.1%[78]	[78]
Lack of emotions	17.6%[78]	[78]
Lability	17.4%[91] to 40.4%[78]	[78,91]
Violence	15%[101] to 35%[86]	[86,101]
Hostility	72%[80]	[80]
Irritability	10%[34] to 36.9%[91]	[34,91]
Psychomotor agitation/excitement	80%[98] to 90%[96]	[96,98]
Psychomotor retardation/slowness	36.8%[78] to 46.2%[54]	[54,78]
Catatonia	16.6%[46] to 20%[47]	[46,47,91]
Elation/hypomania/manic	9%[80] to 40.4%[78]	[54,78,80,96]
Depressed mood/sadness/tearfulness	10%[96] to 87%[80]	[54,66,78,80,91,96]
Worries	27%[80]	[80]
Obsessive-compulsive symptoms	15.4%[54]	[54]
Anxiety	45%[66] to 83%[53]	[53,66]
Suicidality	14%[78] to 55.17%[103]	[46,54,78,101,103]
Suicide attempt	10.9%[91] to 20.7%[103]	[91,103]
Infanticidality	30.7%[46]	[46]
Poor attention	98%[66]	[66]
Poor concentration	86%[80] to 98.2%[78]	[78,80]
Lack of insight/judgment	100%[66]	[66]
Confusion/perplexity	10%[96] to 92%[53]	[53,91,96]
Altered biofunctions	92.3%[54]	[54]
Sleep disturbance	90%[80] to 100%[53]	[53,62,80]
Appetite disturbance	90%[80] to 95.6%[62]	[62,80]
Autonomic disturbance	63%[80]	[80]

AH: Auditory hallucination, SFRS: Schneiderian first-rank symptom

Comorbidities

Most studies have usually not reported the prevalence of medical comorbidities in patients with ATPD. Occasional studies that have estimated the prevalence of medical comorbidities in patients with PPP have reported it to be 23.1%; however, this study did not report the prevalence of medical comorbidities, specifically in patients of PPP with ATPD.[54] In adolescents considered for ECT, comorbid medical illnesses like seizure disorder, hypothyroidism, and others like urachal cysts have been reported.[51] But again, this study did not report the prevalence specifically among patients with ATPD.

Substance use as a comorbidity has been studied in several studies.[42,43,45,49,58,72,73,75,85,100,101,107] Tobacco,[43,45,58,72,75,101] alcohol,[43,45,58,100,101,107] and cannabis[45,58,100,107] are the commonly used substances reported in most of these studies as use, problem use, misuse, or use disorder/dependence. Opioid abuse in 3.2%[107] and inhalant abuse in 0.7%[45] of the sample were reported. Although the studies showed a high prevalence of psychoactive substance abuse compared to the general population,[58] the use of illicit drugs was substantially less in patients with ATPD when compared to developed countries.[45]

Comorbid depression in 28% and obsessive-compulsive disorder in 24% among inpatients of non-affective FEP have been reported in one study.[42]

Studies focusing on treatment

Psychotropics

Some studies have evaluated the efficacy/effectiveness of haloperidol,[63,99,102] olanzapine,[76] and risperidone[99] in ATPD. The sample size of these trials ranged from 23[76] to 40,[102] and the duration of these trials ranged from 2[63] to 6 weeks.[76] The outcome was evaluated using BPRS,[63,76,99,102] Clinical Global Impression (CGI),[63,76] and Global Assessment of Functioning (GAF).[99]

The oldest trial[102] that compared the low (5 mg/day) and high (20 mg/day) doses of haloperidol revealed no significant difference in the efficacy as assessed on BPRS. A single-blind randomized controlled trial (RCT)[99] that compared risperidone 4 mg/day and haloperidol 15 mg/day for four weeks in 30 patients showed risperidone to be significantly better than haloperidol in management of ATPD with outcome assessed using BPRS. It was also noted that risperidone had earlier onset of action in some positive and negative symptoms. A double-blind, randomized trial that included 60 drug naïve acute psychotic patients compared intramuscular haloperidol or levosulpiride injection in the initial 5 days reported haloperidol superior for overt aggression, possibly for psychotic symptoms.[209,210]

Another study reported the safety and efficacy of olanzapine (5-20 mg/day) for six weeks in an open trial that involved 23 children and adolescents with ATPD.[76] Another study that compared aripiprazole (10-15 mg/day) and haloperidol (10-15 mg/day) in a 4-week open-label trial in 30 patients with childhood and adolescent psychotic disorders, including ATPD reported aripiprazole to be as efficacious as haloperidol in improving positive and negative symptoms with better tolerability.[211]

Regarding side effects, the study that compared haloperidol and risperidone showed that all subjects in the haloperidol[99] group experienced extrapyramidal symptoms (EPS) compared to 40% in the risperidone group. However, more subjects receiving risperidone required propranolol for akathisia or benzodiazepines for lack of sedation. The study that evaluated olanzapine in children and adolescents reported dryness of mouth in 61% of the participants and increased appetite and weight gain in 52% of the participants.[76]

An RCT[63] that included 24 patients evaluated the role of add on Vitamin E (3200 IU/day) to 10 mg/day haloperidol for two weeks. The authors failed to show any prophylactic effect of the same on drug-induced EPS when compared to the group receiving only haloperidol.

Another study that evaluated the side effects of aripiprazole (2.5–15 mg/day) in 30 children and adolescents with psychotic disorders, including brief psychotic disorder, reported acute dystonia (25%), sedation, fatigue, akathisia (16%), and other side effects.[212]

Other side effects of psychotropics reported in case reports involving patients with ATPD include EPS with aripiprazole,[213] neuroleptic malignant syndrome (NMS) with olanzapine,[214,215] aripiprazole,[216] and injection haloperidol,[217] NMS in the absence of raised creatinine phosphokinase levels,[218] psoriasis with olanzapine,[219] acute pedal edema,[220] and angioneurotic edema[221] with risperidone, hirsutism with olanzapine,[222] cognitive decline amounting to dementia in an elderly patient of ATPD after being treated with olanzapine, lorazepam, and trihexyphenidyl.[223]

Electro convulsive therapy (ECT)

The studies on ECT in adolescents with psychiatric disorders,[51] postpartum syndromes,[46,54] and other psychiatric disorders[52] have provided some information about ATPD. The sample size of ATPD in these studies ranged from 1[54] to 22.[52] Of these, one was a naturalistic prospective study,[46] and three were retrospective studies.[51,52,54]

The effectiveness of ECT in postpartum psychiatric syndromes has been evaluated in a naturalistic prospective study[46] that included 20 patients of ATPD among 78 other postpartum syndromes. It was seen that bitemporal-modified ECT decreased the duration of admission and decreased CPRS scores, but the results were not statistically significant when compared to the group that did not receive ECT. However, data specific to the ATPD subgroup were not available. In a 13-year retrospective study that included one patient of ATPD among 13 other postpartum syndromes, ECT was found to be safe, effective, and associated with minimal complications.[54] Another 5-year retrospective record-based study on ECT that included 22 patients of ATPD among 148 patients with other severe mental illnesses showed that females with ATPD and mood disorders required a more significant number of ECT sessions than their male counterparts, but with no statistical difference.[52] Another retrospective study that included 20 patients with ATPD showed that the mean number of ECTs required by patients with ATPD is eight, and the use of ECT was associated with significant clinical improvement.[224]

The 12-year retrospective chart review on ECT in adolescents with severe psychiatric disorders (two patients with ATPD out of 25) showed that ECT is effective and is associated with the same frequency of side effects as adults.[51] The response rate of ECT in ATPD was 77.7 (SD: 31.6), with a range of 55–100, which was higher than the response to schizophrenia and schizoaffective disorder but lesser than that of depression, psychosis NOS, and organic catatonia.[51] Some case reports also mention using ECT to treat catatonic symptoms associated with ATPD in special conditions like retinitis pigmentosa,[151] young age,[215,225,226] and postpartum period,[227] respectively.

Pathway to care

A study that evaluated the pathways to care of 151 patients of FEP (ATPD = 40) showed that pathways to psychiatry care are complex and multidirectional.[44] Out of 60 patients of FEP, an assessment of pathways to care revealed that only 18.3% had their first contact with a psychiatrist, whereas 55% had first contact with a faith healer. On average, the first contact ever was initiated two months after illness onset.[228] Duration of untreated psychosis (DUP) in FEP patients was 124.93 weeks (SD: 122.13), with longer DUP in married, old age, and uneducated patients.[229]

Others

Adherence-focused structured psychoeducation was likely to improve adherence in the long term in patients with FEP compared to treatment as usual.[230] Treatment by traditional methods like faith healing leading to loss of vision[231] and successful management of ATPD using homeopathic medication[232] have also been reported in some of the case reports.

Studies focusing on course and outcome

Twenty-two studies have reported details of the course and outcome of patients of ATPD[33,49,60,62,69,78,79,81,85,90,92,93,94,95,97,100,101,104,233,234,235,236] [Table 6]. Among these, patients have been followed up for variable duration with studies reporting course and outcome at 3 months,[79] 6 months,[69,78,79,92,235] one year,[79,90,101,95,33,235] 2 years,[90,101] 3 years,[62,81] 5 years,[49,60,234] 8 years,[233] 10 years,[85,97,104,236] and 12 years.[93] One study did not mention the duration of follow-up but provided the mean duration of follow-up to be 13 months[94] (SD: 11.7).

Table 6.

Course and outcome of ATPD

Author	Outcome at first follow-up	The outcome of the second follow-up
Brar et al., 2022[79]	6m	1y
	-LTFU (26.6%)	-LTFU (50%)
	- The outcome of those available for follow-up	-The outcome of those available for follow-up
	- Remission (63.64%)	- Remission (50%)
	- Recurrence (11.36%)	- Recurrence (10%)
	-Schizophrenia (11.36%)	-Schizophrenia (13.33%)
	- Depression (9.09%)	-Depression (26.67%)
	- Mania (4.55%)
Chandak & Gowda, 2017[78]	6m
	-No change (73.6%)
	- Other psychosis (15.8%)
	- Schizophrenia (5.2%)
	- Dissociative disorder (1.8%)
	-Depression (1.8%)
	- Bipolar disorder (1.8%)
Chaturvedi & Sahu, 1986[81]	3y -No change (55.2%)
	- Diagnostic change (44.8%)
	-Schizophrenia (8.6%)
	- Manic-depressive psychosis (20.7%)
	- Reactive and others (15.5%)
Chavan & Kulhara, 1988[69]	6m
	-No change (86.4%)
	- Depression (9.1%)
	- Schizophrenia (4.5%)
Gupta & Bhardwaj, 2000[85]	10y
	-Complete remission (74.2%)
	-Bipolar disorder (8.1%)
	- Schizophrenia (9.7%)
	- ATP (56.4%)
	-Rest (25.8%)
	-Continuous illness (16.1%)
	- Initially remitted, then continuous illness (9.7%)
Kar & Dhanasekaran, 2017[100]	3m
	-Follow-up (65.7%)
	- The outcome of those available for follow-up
	- Remission (66.3%)
	- Change in diagnosis (33.7%)
	-Mood disorder 14.13% (9.78%: Manic episode, 4.35%: Depressive episode)
	-Schizophrenia spectrum 18.48% (5.43%: Schizophrenia, 13.04%: Other non-organic Psychosis)
	-Dissociative disorder (1.08%)
Narayanaswamy et al., 2012[90]	1y	2y
	-Follow-up (77.2%)	-Follow-up (75.4%)
	- The outcome of those available for follow-up	-The outcome of those available for follow-up
	-Relapse (47.4%)	-Diagnosis:
	- Diagnosis:	-No change (63.2%)
	-No change (70.2%)	-Bipolar disorder (21.1%)
	- Bipolar disorder (14%)	-Schizophrenia (8.8%)
	- Schizophrenia (8.8%)	-Psychosis NOS (7%)
	- Psychosis NOS (7%)
Rajkumar, 2015[101]	1y	2y
	-Relapse (50%)	-Relapse (65%)
Sajith et al., 1999[92]	6m
	-ATPD (70%)
	- Schizophrenia (30%)
	- Delusional disorder (7.5%)
	- Mania (2.5%)
	- Depression (1.3%)
	-Psychosis NOS (13.8%)
Sajith et al., 2002[62]	3y
	-ATPD (73.3%)
	- Bipolar disorder (22.2%)
	- Psychosis NOS (4.4%)
Susser et al., 1998[93]	12y
	-Recovery (82.3%)
	- Recurrence (11.7%)
	- Persistent illness (6%)
Thangadurai et al., 2006[94]	13m (SD: 11.7) -Affective disorder (9.2%) - Schizophrenia (26.4%) - Recurrent episodes of ATPD (11.5%)
Varma et al., 1996[95]	1y
	-Full remission (70%)
	- No remission (10%)
	- Full remission with relapse (13%)
	- Partial remission (5%)
	-Partial emission with relapse (1%)
ICMR study, 1985[33]	1y
	-No change (35%)
	- Manic-depressive psychosis (29%)
	- Other non-organic psychosis (36%)
Malhotra et al. 2005[233] $	8y
	-Recurrence (46.6%)
Janardhanan et al., 2010[235] $	6 m
	-Follow-up (75.4%)
	- Diagnostic change (33.3%)
	-Bipolar disorder (36.8%)
	- Psychosis NOS (36.8%)
	- Schizophrenia (26.3%)	1y -Follow-up (64.9%)
Vhm et al., 2017[236] $	10y
	-Single episode 38%
	- Relapse 62%
	-2nd episode of ATPD (41%)
	- Schizophrenia (17%)
	- Bipolar disorder (21%)
Mishra et al., 2022[97,104] $	10y
	-Remission (44.2%)
	- Relapse to other chronic illnesses (51%)
	- Mean duration to a diagnosis of
	-Psychotic illness (3.84 years, SD: 3.5)
	- Bipolar disorder (4.04 years, SD: 3.8)
Mukherjee et al., 2015[49] $	5y
	-Stable diagnosis (51%)
	- Change in diagnosis
	-Schizophrenia (22%)
	- Bipolar disorder (12.3%)
Lukose et al., 2014[60] $	5y
	-Change in diagnosis (37.8%)
	-Schizophrenia (14.6%)
	- Bipolar disorder (13.4%)
	- Severe depression (2.4%)
	- Episodic psychosis (2.4%)
	-Psychoses NOS (1.2%)
	- Schizoaffective disorder (1.2%)
	- Recurrent depressive disorder (1.2%)
	- Mania with psychosis (1.2%)
Rozario et al., 1999[234]#	5y -Recurrence (35%)

LTFU: Lost to follow-up, ATPD: Acute and transient psychotic disorder, m: month, y: year. ^$data from published conference abstract, ^#data from an unpublished thesis

Recurrence

The available studies suggest that a proportion of patients do experience recurrence of episodes of ATPD. Studies of shorter duration have estimated the recurrence rates to be 10%[79]–11.7%.[93] In contrast, a long-term follow-up study estimated the recurrence rate to be 46.6% at 8-year follow-up,[233] and another study reported the recurrence rate to be 35%[234] at five years [Table 6].

Diagnostic change

Data from these studies also suggest that in less than one-third of the patients, the diagnosis of ATPD is revised to schizophrenia[49,60,69,78,79,81,85,90,92,94,100,235,236] or other schizophrenia spectrum disorders,[33,60,62,78,81,90,92,97,100,104,235] bipolar disorder (of either polarity)[33,49,60,62,78,79,81,85,90,92,94,97,100,104,235,236], depression,[60,69,78,79,92,94,100] and dissociative disorders[100] [Table 6].

Malhotra, 2016[237] studied factors that affected diagnostic instability in ATPD and found early age of onset, lower level of education, unskilled or semiskilled occupation, lower socioeconomic status, negative family history, treatment with only antipsychotics, and not taking treatment for more than four months regularly to predict a more likely diagnosis of schizophrenia and the opposite factors for bipolar disorder. In adolescents, precipitating stress, the severity of illness, the need for hospitalization, and longer normal intermorbid periods between initial episodes resulted in a change in diagnosis.[60]

Diagnostic stability was found more in married people, those with abrupt onset, and polymorphic subtypes. Those with schizophrenia symptoms were significantly more likely to be re-diagnosed as schizophrenia than those with polymorphic symptoms.[49]

Other outcomes

One of the studies suggested that patients with onset of illness at or after the age of 20 years and those who were married showed early response to treatment and had a favorable clinical outcome.[73] Another study that involved patients with FEP (all of whom were not diagnosed with ATPD) showed significant improvement in performance in Wisconsin Card Sorting Test (WCST), Spatial Working Memory Test (SWMT), and Continuous Performance Test (CPT) following recovery from the acute psychosis at 3 months.[70,238] However, other studies noticed significant differences between FEP in general[239,240,241,242] or FEP in remission[243,244] and healthy controls in various neurocognition and social cognition domains. Two additional studies that assessed the social cognition of patients with FEP in remission showed partial improvement in social functioning,[64] with impairment in domains of the second-order theory of mind after the resolution of symptoms.[71] Another study showed that female patients of FEP have significantly more improvement in cognitive insight than males. It was also found that more improvement was seen in patients with a diagnosis of ATPD when the illness was of lesser duration at baseline and when a precipitating factor was present.[245] A study on females with PPP found deranged higher mental functions.[246] Studies also observed the increased period of untreated illness and poor premorbid functioning to predict clinical presentation, including the severity of psychotic illness, prolonged treatment, and increased burden in FEP[247,248].

The neurodevelopmental hypothesis in the outcome of FEP was proven by a study that found that the average right DLPFC volume was higher in good responders and that smaller DLPFC volume predicted clinical and sociofunctional outcomes significantly[249].

A 10-year follow-up study of 101 patients of FEP found predictors of good recovery to be high baseline positive symptoms, low negative symptoms, higher anxiety-depressive symptoms, lower level of depressive symptoms, lower aggression, higher work performance, and the ability for independent living. At the same time, non-recovered patients showed higher EPS, severe aggression, higher disorganization, and family burden.[250]

Review articles on ATPD

We found eight review articles on ATPD written by authors of Indian origin. Two articles mention the contribution of Indian psychiatry to the world in the form of research on ATPD.[251,252] Two other reviews explain how ATPD as a group is different from schizophrenia.[253,254] Udomratn et al.[255] discussed the status of ATPD in Asia. In contrast, Malhotra et al. 2019[256] discussed the ongoing worldwide research on ATPD, including the current understanding of nosology, epidemiology, clinical description, genetics, and neurobiology, thereby evaluating its distinctiveness as a group. Other review articles have focused on specific areas like epidemiology,[257] diagnostic stability,[258] and treatment[257] of ATPD.

DISCUSSION

This review article suggests that many studies have emerged on ATPD from India. Before ICD-10, the majority of the studies focused on validating the diagnosis of ATPD. These initial studies clearly showed the existence of a third psychosis, i.e. a psychotic condition other than schizophrenia and manic-depressive psychosis. Further, these studies provided information about specific characteristics of ATPD, such as having abrupt to the acute onset and good outcomes. These studies and similar studies across the globe contributed to the inclusion of ATPD in ICD-10. These initial studies also suggested that in ATPD samples, females out-number males, and a higher proportion of patients with ATPD are from rural backgrounds.

Additionally, it was reported that ATPD is associated with childbirth, fever, and season. However, many of these studies have not included a control group. Hence, it is difficult to make any conclusion. However, the present review suggests that when the data from different studies are pooled, there is a slight preponderance of males, and the majority of subjects with ATPD are married, from lower socioeconomic status, rural locality, nuclear family setup, and are Hindu by religion. Regarding occupation, those who are unemployed or homemakers together form the largest group.

Regarding prevalence, the multisite ICMR study reported that patients with ATPD form 8.7% of the total psychosis patients.[33] Besides this study, there was a general lack of data on studies explicitly evaluating the prevalence of ATPD. However, when we attempted to assess the prevalence of ATPD studies focusing on other research queries, it is evident that the prevalence of ATPD varies across different study settings, with a prevalence of 1.7%[39] to 2.26%[37] in all new outpatients, 3.2% among the adult inpatients,[57] and 2.3% among the psychiatry patients referred to psychiatry emergency services.[41] The prevalence of ATPD among FEP patients varies from 14%[43] to 26.5%[44] and 25.6%[46] to 61%[55] in females with PPP[46] and is 39% among postpartum females with catatonia.[47] These data suggest that ATPD form a tiny proportion of all the new patients seen in the walk-in. However, it is essential to note that all these studies have not explicitly focused on the prevalence of ATPD. Hence, it can be said that there is an urgent need to evaluate the prevalence of ATPD across different treatment settings systematically.

Regarding clinical profile, most of the data suggest that patients with ATPD have abrupt to acute onset of illness,[39,46,51,53,54,62,66,67,70,78,79,85,91,101] and stress is associated with the start of illness.[61,66,67,74,80,82,195,196] Other factors, which have been reported to be associated with ATPD, include season (summer peak)[61,73,105], fever,[61,67,73,82,83,88] and childbirth.[61] However, more data is needed on these variables as many of the studies that have reported such associations have not included a control group. Although data on postpartum females suggest a higher prevalence of ATPD,[46,47,48,54,55] there is a lack of case-controlled data to make such an association. Similarly, for data from India, no consistent personality profile can be associated with ATPD. However, it is essential to note that these differences could be due to different assessment instruments. Although an attempt has been made in some of the studies to evaluate the immunological markers associated with ATPD, the findings have remained inconsistent.

Only 16 studies[35,49,60,72,76,78,79,84,91,92,93,98,99,100,101,102] provided information about various subtypes of ATPD as per the ICD-10, and the prevalence of these was variable across the different studies. The findings that the multiple subtypes are less frequently used in research may reflect similar lower use of subtypes in routine clinical practice. Hence, it can be said that the removal of various earlier described subtypes from ICD-11 could be attributed to this lower use.

More data on the symptom profile of ATPD from India need to be collected. This could be attributed to the lack of specific scales to assess the symptoms, including the polymorphic picture. However, it can be argued that various scales, such as BPRS and PANSS, can be used to evaluate the symptom profile of ATPD, and an attempt must be made in the future to understand the symptom profile of ATPD in the Indian context.

Although conventionally, antipsychotics are used for the management of ATPD, there is a lack of data from India and other parts of the world regarding the efficacy/effectiveness of various antipsychotics. Although preliminary data suggest the beneficial effect of ECT among patients with ATPD, the data are not sufficient enough to make any recommendations for its use in patients with ATPD.

Compared to other aspects, reasonable data are available on the diagnostic stability and recurrence of ATPD across different studies. These data suggest that in a large proportion of patients initially diagnosed with ATPD, the diagnosis remains stable. This percentage reported in Indian studies is comparable to data from other parts of the globe.[259] Similarly, when we compare the stability of the diagnosis of ATPD with diagnostic stability for schizophrenia and bipolar disorder,[260,261] it can be said that it is comparable. Accordingly, it can be said that based on the diagnostic stability, ATPD emerges as a separate diagnosis. In terms of recurrence rates, studies from India have suggested that in the short term, the recurrence rates are 10%[79]–11.7%,[93] and in long-term follow-up, the recurrence rate varies from 35%[234] to 46.6%.[233] Accordingly, it can be said that these data from India[33,49,60,62,69,78,79,81,85,90,92,93,94,95,97,100,101,104,233,234,235,236] and from other parts of the globe[259] have led to the inclusion of recurrent ATPD in ICD-11.

It is important to note that the present review suggests certain limitations of data emerging from India. Except for the initial ICMR study,[33] there is a lack of multicentric studies, and the sample sizes of most studies are limited. Additionally, there are little data on the symptom profile of ATPD. Similarly, various treatment aspects of patients with ATPD are also limited, which makes it difficult to recommend the duration of pharmacotherapy. Although some data are available on risk/precipitating factors, the data need more consistency. Accordingly, we need to evaluate symptom profiles, course, outcomes, and treatment outcomes in patients with ATPD using validated instruments to improve our understanding. Further, there is a need for comparative studies to evaluate the risk factors for ATPD. The sampling technique reported in some of the studies can also be questioned. Future studies must attempt to overcome these limitations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.