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RISPERDAL® (risperidone)

Medical Information

Adverse Event of RISPERDAL- Pituitary Tumors

Last Updated: 08/05/2025

Summary

  • Pituitary adenoma has been reported since market introduction.1
  • In a pharmacovigilance study by McCarren et al (2012), risperidone did not appear to have an increased risk in the incidence of medical records validated pituitary tumors with mass effects compared to other atypical agents (event rates: 2.5/100,000 person-years, each).2
  • Szarfman et al (2006)3 analyzed the disproportionality of reporting of pituitary tumors, hyperprolactinemia, and galactorrhea in patients treated with risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol using the FDA’s Adverse Events Reporting System (AERS) database between January 1968 and May 2005. The highest adjusted reporting ratios for pituitary tumor, hyperprolactinemia, and galactorrhea were with risperidone. These data may represent an adverse event signal, but do not establish a causal relationship.
  • Several case reports4-16 have identified pituitary adenomas detected in patients while on risperidone, with authors recommending that further research is needed to explore whether a relationship between pituitary tumors and antipsychotics may exist in humans. In most cases, clinical symptoms potentially related to hyperprolactinemia resulted in an endocrinologic evaluation, including MRI (magnetic resonance imaging) or CT (computerized tomography), for assessment of pituitary abnormalities.

BACKGROUND

Pituitary tumors commonly occur in the general population (10-25% incidence) and are located beneath the base of the brain; 99% are benign (McDowell17; The Neuroendocrine Clinical Center and Pituitary Tumor Center18). Pituitary tumors are sometimes serendipitously noted during a CT or MRI exam that was performed for other reasons (Mavrakis 2004)19. Although the majority of pituitary tumors are small (less than 10 mm in greatest diameter) and clinically silent, some pituitary tumors may be hormonally active and cause associated symptoms (e.g. prolactin production) or grow large and cause symptoms by compressing neighboring structures (“mass effect”). Symptoms include headaches (which can occur with small or large tumors) and vision problems.

PRODUCT LABELING

Please refer to the following sections of the enclosed Full Prescribing Information that are relevant to your inquiry: WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS.

CLINICAL DATA

Double-Blind Trials

Koenigsberg et al (2003)20 conducted a 9-week, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of low dose risperidone (starting dose 0.25 mg/day, titrate up to 2 mg/day) in 25 patients with schizotypal personality disorder (SPD). Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), Schizotypal Personality Disorder Questionnaire, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale.

  • Overall, low-dose risperidone was effective in reducing symptom severity and was well tolerated in these patients.
  • One patient developed galactorrhea at a 1-mg dose, and her risperidone dose was lowered to 0.5 mg/day and then 0.25 mg/day before she was terminated from the study. Endocrinologic evaluation later revealed a pituitary microadenoma.

Pharmacoepidemiologic Studies

Johnson & Johnson Research and Development designed the protocol for a pharmacoepidemiologic study (with agreement from FDA on the definition of the primary outcomes) to examine the relationship between risperidone and pituitary tumors with mass effect. McCarren et al (2012)2 utilized Optum Insight Life Sciences Research Database (LSRD; 01 July 2002 to 31 December 2007) and the Department of Veterans Affairs (VA) medical care databases (01 June 1999 to 30 September 2009), to compare the association of risperidone (and other atypical antipsychotics) with pituitary tumors with mass effects.

Study Design/Methods

  • Retrospective, nested, case-control study with a cohort of patients treated with ≥2 consecutive (≤3 months between prescriptions) antipsychotic dispensations (risperidone versus other atypicals versus conventional antipsychotics).
    • Exclusion criteria included: pharmacy claim for prescribed drug 6 months prior to first dispensation; medical claim consistent with malignancy or pituitary tumor prior to first drug exposure
    • Cohort follow-up period began at the index date (start of second dispensation) and lasted until censoring event (pituitary tumor diagnosis; last claim in database; 9 months before a pregnancy code) or end of study, whichever came first.
  • Pituitary tumor with mass effects: Medical diagnosis of a pituitary tumor plus one of the following: pituitary surgery, pituitary radiation therapy, visual field disturbances or pituitary hormone deficiency.
  • Primary cohort analysis: Incidence rates of pituitary tumors with mass effects (confirmed by medical records) between risperidone and other atypicals (cox proportional-hazards regression model; adjusted for age only due to limited number of confirmed cases).
    • Secondary outcomes:
      • Case-control analysis: Calculated ORs for pituitary tumors with mass effects (confirmed by medical records) comparing risperidone to other atypicals (conditional logistic regression model).

Results

  • In patients treated with atypical antipsychotics, the incidence of validated pituitary tumors with mass effects was comparable to that of the general population (1.4 -2.5 per 100,000 person-years versus 2.8 per 100,000 person-years, respectively) (Table: Pituitary Tumor Analyses – VA and LSRD Databases).
    • Compared to other atypical agents, risperidone did not appear to have an increased risk in the incidence of medical records validated pituitary tumors with mass effects.

Pituitary Tumor Analysis - VA and LSRD Databases
 
Risperidone
Other Atypicals
Total Subjects in Cohort
VA (electronic database)
156,324
183,250
LSRD (claim-based database)
21,386
48,863
Cohort Analysis
All Pituitary Tumors
VA (electronic database)
492
315
LSRD (claim-based database)
28
45
 
 
 
Pituitary Tumors with Mass Effects (Medical Records Validated)
VA
20
19
LSRD
0
1
Crude Incidence Rates/100,000 Person-Years
VA
2.5
2.5
LSRD
0
1.4
Adjusted Hazard Ratios (95% CI)
VA
1 (0.5-1.9)
Reference
Case Control Analysis
Odds Ratio (95% CI) for pituitary tumors with mass effects (confirmed by Medical Records)
VA
1 (0.5-2)
Reference
Abbreviations: LSRD, Life Sciences Research Database; VA, Veterans Affairs.

EudraVigilance European Pharmacovigilance Database

Lertxundi et al (2018)21 analyzed the relationship between atypical antipsychotics and pituitary tumors in the EudraVigilance European pharmacovigilance database.

Methods/Results

  • The search included all suspected spontaneous cases of pituitary tumors associated with atypical antipsychotics up to 23 March 2017 in EudraVigilance. The association between tumor and drug was assessed by calculating proportional reporting ratios (PRRs).
  • After deduplication, 292 cases were assessed (72% were women; median age was 36 [range, 5-73] years).
    • PRR was the highest for amisulpride (51.57; 95% CI, 36.3-73.2), followed by risperidone (21.83; 95% CI, 18.4-25.8) and its metabolite paliperidone (19.95; 95% CI, 14.7-27.1).
    • Risperidone was the most frequently implicated drug in generating a safety signal, with 156 reported cases, of which 24 were reported with the depot formulation.

Claims-based Study

Gianfrancesco et al (2009)22 discussed the potential bias in testing for hyperprolactinemia and pituitary tumors in risperidone-treated patients in a claims-based study.

Methods/Results

  • Two databases (large commercial; Medicaid) were utilized to identify treatment episodes with risperidone, clozapine, olanzapine, quetiapine, ziprasidone, aripiprazole, haloperidol, perphenazine, and “other typical” (reference group) antipsychotics.
  • Analysis of 197,926 treatment episodes revealed that among the antipsychotics, risperidone was associated with a significantly greater likelihood of prolactin assessment in patients with or without preceding prior potentially prolactin-related adverse events (Hazard Ratio (HR): 1.34, 95% Confidence Interval (CI): 1.09-1.66; p=0.007).
  • A significantly higher likelihood of an MRI/CT was observed in patients with hyperprolactinemia or prior potentially prolactin-related adverse events receiving risperidone (OR (odds ratio): 1.66, 95% CI: 1.23-2.23; p=0.001) or ziprasidone (OR: 1.66, 95% CI: 1.06-2.62; p=0.028).
  • The authors concluded that the disproportionate identification and reporting of pituitary adenomas in risperidone-treated patients may be a result of more evaluations in this patient population.

WHO ADR Database

Doraiswamy et al (2007)23 reviewed reports of pituitary neoplasms in the WHO ADR (adverse drug reaction) database for risperidone and amisulpride.

Methods/Results

  • The authors generated two IC (information component) scores:
    • IC (a measure of the strength of the dependency between a drug and an ADR)
    • IC025 (value of the lower 95% confidence limit for the IC)
  • In the WHO ADR database, risperidone had the second highest IC score for pituitary neoplasm benign (IC=4.03, IC025=3.33, 19 reports) and pituitary neoplasm NOS (IC=4.49, IC025=3.86, 23 reports).
  • The authors noted that IC scores do not indicate causality, but provide a measure of a disproportional relationship of a drug-ADR combination within the database.

FDA Adverse Events Reporting System (AERS) Database

Szarfman et al (2006)3 analyzed the disproportionality of reporting of pituitary tumors, hyperprolactinemia, and galactorrhea in patients treated with risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol using the FDA’s AERS database between January 1968 and May 2005.

Methods

  • The Multi-item Gamma Poisson Shrinker (MGPS) statistical algorithm was applied to detect higher than expected drug-event associations (“signals”) within the AERS database.
  • The authors searched the database for the following event codes: pituitary tumor, prolactinoma, pituitary tumor benign, blood prolactin increased, hyperprolactinemia, gynecomastia, breast hypertrophy, amenorrhea, and galactorrhea.
  • Estimated prescription data from launch of antipsychotic drug through June 2005 was obtained from the IMS National Prescription Audit Plus database.  No controls were used for the length of time of commercial availability for each of the medications.

Results

  • Seventy-seven pituitary tumor reports were identified, with 54 reports associated with risperidone.  Women accounted for 82% of all reports.
  • Risperidone had the highest adjusted reporting ratios (disproportionality signal scores) for pituitary tumors, hyperprolactinemia, and galactorrhea, followed by haloperidol, ziprasidone, and olanzapine.
  • Table: Number of Reported Pituitary Tumors displays the number of pituitary tumors reported with each of the seven antipsychotics evaluated.
    • The numbers reported below account for patients who may have been using more than one antipsychotic at a time, though only 20% of risperidone reports noted concomitant use of another antipsychotic or other suspect drug.
    • Approximately 50% of the tumors were identified as benign, with pituitary tumor complications reported with risperidone (n=14), haloperidol (n=4), clozapine (n=3), and olanzapine (n=1).

Number of Reported Pituitary Tumors
Antipsychotic
Number of reported pituitary adenomas
Risperidone
54
Haloperidol
9
Ziprasidone
6
Olanzapine
11
Clozapine
4
Quetiapine
1
Aripiprazole
0
  • Three adolescents (age 14-16 years) treated with risperidone, and 1 child/adolescent treated with olanzapine were reported to have a pituitary tumor.  While reports of hyperprolactinemia or galactorrhea occurred more frequently with risperidone as compared to the other antipsychotics in younger children (age <7 years), more than 90% of cases were in adolescents.
  • Data from the IMS National Prescription Audit Plus showed that ziprasidone (6/5,672,000) had the highest total number of reported pituitary tumors relative to prescription volume, followed by risperidone (43/80,987,000), olanzapine (7/62,795,000), and others.

Limitations

  • The authors identified several key study limitations:
    • Risperidone’s known association with elevation of prolactin levels may have led to more frequent pituitary investigations, resulting in a detection bias.
    • The AERS database search cannot establish causality; thus, the results of this analysis cannot be used for this purpose and are preliminary.
    • Further investigation, using additional methods, is required to better determine why the numerical differences between the atypical antipsychotic agents were observed.
    • Pharmacovigilance reporting may be influenced by detection and reporting biases inherent in the AERS database.
  • Additional AERS database limitations included:
    • Changes in reporting and collection methodology over time
    • Differential underreporting
    • Potential differences in co-morbidities or concomitant medications among exposed patients
    • Inability to completely eliminate duplicate reporting
    • Incomplete case histories.
  • The authors concluded that treatment with antipsychotics may be associated with pituitary tumors, but additional epidemiologic studies, long-term comparative studies, and detailed analyses of pituitary tumor cases associated with antipsychotics are necessary to ascertain causality and relative risk.

Case Reports


Case Reports
Background
Outcomes
Rad et al (2019)16 reported the case of a 13-year-old girl initially hospitalized in 2014 for acute psychotic disorder. She was discharged after initiating treatment with risperidone 2.25 mg/day as 2 divided doses and lorazepam for 2 weeks with gradual dose tapering.
  • After 2 months of treatment, psychomotor symptoms persisted, and plasma prolactin levels were 63.2 ng/mL. The symptoms improved over the months, with a risperidone dose reduction to 1 mg/day. However, prolactin levels ranged between 55 and 85 ng/mL at monthly repeated dosing.
  • A brain MRI (conducted after 10 months of risperidone treatment) revealed an 11×8 mm, well defined, homogenous formation suggestive of a pituitary adenoma. Risperidone was then discontinued, and prolactin levels returned to normal after 1 month.
  • After 4 months of risperidone discontinuation, a brain MRI confirmed that pituitary gland structure and thickness were within normal limits and without objectifying adenoma, and prolactin levels were within normal limits.
Arcari (2012)4 reported a case of a Caucasian woman initially hospitalized in 1974 and diagnosed with schizoaffective disorder. Treatment with thioridazine 50 mg daily continued for 21 years until progressive contractions and twitching of various muscles of the tongue, indicative of the possible onset of tardive dyskinesia, prompted a switch to risperidone 2 mg daily at age 57.
After successful treatment with risperidone 2 mg daily for 10 years, a serum prolactin level of 83.8 µg/L was reported in June 2005. A cranial MRI showed evidence of a suspicious 2 mm area of the pituitary gland consistent with microadenoma. A second prolactin level of 110.1 µg/L was reported in August 2005. In October 2005 the patient was tapered off risperidone and slowly transitioned to ziprasidone by increasing with 40 mg increments to a dose of 80 mg twice daily by November 28th, 2005. Prolactin levels dropped to 41.7 µg/L one month after beginning the switch to ziprasidone (November 10, 2005), dropped to 11.7 µg/L on December 15, 2005 and remained normal over the following 5.5 years. A follow-up MRI in May 2006 revealed no evidence of the adenoma. The patient, however, experienced periods of instability on ziprasidone.
Ng et al (2010)5 reported the case of a 29-year-old Singaporean female diagnosed with paranoid schizophrenia and treated with risperidone or olanzapine at various times.
-Upon a second hospital admission, persistent persecutory delusions and new onset of visual hallucinations, while on risperidone 6 mg/day, prompted a CT of the brain.
  • Results showed a homogenous pituitary mass with MRI confirmation of a long-standing pituitary macroadenoma (expansions to sphenoid and left cavernous sinus and optic chiasma).
  • Abnormal laboratory Results included: Prolactin level: 13,588 mIU/L (premenopausal: 64-575 mIU/L); PEG Prolactin level: 84% (>60% predictive of monomeric prolactin).
  • Risperidone treatment was switched to aripiprazole 15 mg nightly. Bromocriptine was initiated at 0.625 mg and titrated to 2.5 mg nightly for 5 weeks.
  • Patient was discharged upon stabilization and managed as an outpatient. Her psychotic illness remitted over a 10-month period. She remains on aripiprazole 15 mg nightly.
Sainani and Cabral (2009)6 reported four cases of pituitary adenomas diagnosed during risperidone treatment.
Case 1: During a 2007 admission, a 33-year-old woman reported galactorrhea and menstrual irregularities since the initiation of risperidone in December of 2006. She had increased prolactin levels and a subsequent CT was suggestive of a pituitary microadenoma (0.6 cm; 1999 CT was normal). Following a switch to aripiprazole, the microadenoma decreased in size (MRI, March 2008), serum prolactin levels gradually normalized, galactorrhea decreased, and her menstrual cycle resumed.
Case 2: A 22-year-old-woman, diagnosed with schizophrenia since 2000, was initiated on risperidone in 2006. A follow-up visit in 2007 revealed elevated serum prolactin levels with no symptoms. Head CT was normal until a repeat in 2008 which was suggestive of a small microadenoma in the pituitary fossa (6x5x4 mm). No follow-up data was provided.
Case 3: A 54-year-old-woman, diagnosed with schizophrenia since 1980, was initiated on risperidone in 2006. Investigations into galactorrhea and amenorrhea, reported in 2006, revealed elevated prolactin levels but a normal CT. The patient experienced a continued rise in prolactin levels and a repeat CT in 2007 was suggestive of a microadenoma (4x6 mm) and cerebral artery aneurysms. No follow-up data was provided.
Case 4: A 41-year-old-man was treated, since adolescence, with several different antipsychotics, including risperidone, for a diagnosis of paranoid schizophrenia with comorbid substance abuse. A CT from 2000 was reported as normal. In 2008, risperidone treatment was restarted. Prolactin levels began to rise and were therefore routinely monitored. A repeat CT in September 2008 was suggestive of a pituitary adenoma. No follow-up data was provided.
Sheldrick and Gründer (2008) reported the case of a 39-year-old woman from Kazakhstan with a history of reduced left eye and left visual field sight prompting a 2003 MRI of her brain to confirm a pituitary gland adenoma with a degree of optic chiasm compression.
  • The patient was treated with bromocriptine 2.5 mg/day which she discontinued 2 months prior to an acute psychotic episode which included auditory hallucinations, paranoid delusions, psychomotor agitation, sleeplessness and disorganized thoughts.
  • The patient was admitted to the hospital, restarted on bromocriptine 2.5 mg/day and initiated on risperidone 2 mg/day. Her prolactin level at admission was 39,160 mU/L and she reported missing her menses for a couple of weeks. Under her current therapy of bromocriptine and risperidone, serum prolactin was still elevated but decreased to 9,400 mU/L.
  • After one week, risperidone was switched to aripiprazole 15 mg/day. Following therapy with aripiprazole and bromocriptine, the patient experienced complete remission of psychotic symptoms, better sleep and a normalized serum prolactin level (159 mU/L) four weeks after admission.
Steinhagen (2007)8 reported a case of a 40-year-old old female who initially presented with auditory hallucinations and a six-month history of worsening depressed mood, crying spells, poor appetite, hypersomnia, poor functioning in daily activities and difficult decision making.
After a six-month treatment course of risperidone 0.75 mg three-times-a-day and citalopram 20 mg daily, and a three-month treatment course of topiramate 25 mg BID, the patient complained of galactorrhea, visual hallucinations of amorphous red and green colored shapes, frequent headaches and continued depressive symptoms. She reported regular menstrual cycles throughout treatment.
  • Lab results revealed elevated prolactin levels (72.1 ng/mL). An MRI revealed a lesion measuring 0.8 X 0.6 X 0.6 cm in the superior aspect of the pituitary gland.
  • All three medications were discontinued.  The patient was then started on aripiprazole 15 mg daily for one week increasing to 30 mg daily.
  • After two weeks on aripiprazole, the galactorrhea resolved and after one month, the prolactin level returned to normal level. After 3 months, the patient was lost to follow up.
  • The author commented that it was unclear whether the pituitary microadenoma was prolactin-secreting or an incidental finding of a nonsecretory lesion. The elevated prolactin level and galactorrhea may have been due to risperidone.
Abbreviations: CT, computerized tomography; MRI, magnetic resonance imaging; PEG, polyethylene glycol.

Additional case reports prior to 2007 have been identified during a literature search and are referenced.9-15

Review Articles

Review articles, identified during a literature search, have been referenced for your convenience.24-26

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 30 July 2025.

References

Show
1 RISPERDAL (risperidone) [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RISPERDAL-pi.pdf
2 McCarren M, Qiu H, Ziyadeh N, et al. Follow-up study of a pharmacovigilance signal: no evidence of increased risk with risperidone of pituitary tumor with mass effect. J Clin Psychopharmacol. 2012;32(6):743-749.  
3 Szarfman A, Tonning JM, Levine JG, et al. Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy. 2006;26(6):748-758.  
4 Arcari GT, Mendes AK, Sothern RB. A risperidone-induced prolactinoma resolved when a woman with schizoaffective disorder switched to ziprasidone: a case report. Innov Clin Neurosci. 2012;9(9):21-24.  
5 Ng K, Lee J, Swapna V. Management of a patient with schizophrenia and underlying pituitary macroadenoma. [letter] Ann Acad Med Singapore. 2010;39(11):868-869.  
6 Sainani A, Cabral S. Risperidone. React Wkly. 2019;1747(1):250-250.  
7 Sheldrick A, Gründer G. Aripiprazole Reduces Serum Prolactin in a Woman with Prolactinoma and Acute Psychosis. Pharmacopsychiatry. 2008;41(04):160-160.  
8 Steinhagen CK. Normalization of prolactin with aripiprazole in a patient with psychotic depression and a comorbid pituitary microadenoma. Psychosomatics. 2007;48(4):350-351.  
9 Freeman B, Levy W, Gorman JM. Successful monotherapy treatment with aripiprazole in a patient with schizophrenia and prolactinoma. J Psychiatr Pract. 2007;13(2):120-124.  
10 Koves IH, Jarman FC, Cameron FJ. Antipsychotic medication and marked hyperprolactinaemia: iatros or true prolactinoma? Acta Paediatr. 2004;93(11):1543-1547.  
11 Lertxundi U, Erezuma I, Hernandez R, et al. Antipsychotics and pituitary tumors: an analysis of the European pharmacovigilance database (EudraVigilance). Int Clin Psychopharmacol. 2019;34(2):89-92.  
12 Mendhekar D, Singh B, Jiloha R. Analysis of risperidone induced galactorrhea. Indian J Psychiatry. 2001;43(suppl 2):58.  
13 Malhotra S, Butler B, Oxenkrug G. Switch from risperidone to olanzapine: normalization of prolactinemia and receding of pituitary adenoma. Biol Psychiatry. 2001;49(8):56S-56S.  
14 Pal JK, Sarino WA. Effect of Risperidone on Prolactinoma Growth in a Psychotic Woman. Psychosom Med. 2000;62(5):736-738.  
15 Shafa R, Patel J, Kalinowski A, et al. Pituitary microadenoma, risperidone and clozapine. presented at: 149th Annual Meeting of the American Psychiatric Association; May 4-9, 1996; New York, NY.  
16 Rad F, Buica AM, Anghel GC, et al. Hormonal imbalance and pituitary adenoma during antipsychotic treatment in an adolescent with bipolar affective disorder. Riv Psichiatr. 2019;54(1):37-39.  
17 McDowell BD, Wallace RB, Carnahan RM, et al. Demographic differences in incidence for pituitary adenoma. Pituitary. 2011;14(1):23-30.  
18 Center MGH a. HMSNC, Center PT. Prolactinomas. https://pituitary.mgh.harvard.edu/Prolactinomas.htm
19 Mavrakis AN, Tritos NA. Diagnostic and therapeutic approach to pituitary incidentalomas. Endocr Pract. 2004;10(5):438-444.  
20 Koenigsberg HW, Reynolds D, Goodman M, et al. Risperidone in the treatment of schizotypal personality disorder. J Clin Psychiatry. 2003;64(6):628-634.  
21 Lertxundi U, Erezuma I, Hernandex R, et al. Antipsychotics and pituitary tumors: an analysis of the European pharmacovigilance database (EudraVigilance). Int Clin Psychopharmacol. 2018;34(2):89-92.  
22 Gianfrancesco FD, Sajatovic M, Tafesse E, et al. Association between antipsychotic combination therapy and treatment adherence among individuals with bipolar disorder. Ann Clin Psychiatry. 2009;21(1):3-16.  
23 Doraiswamy PM, Schott G, Star K, et al. Atypical antipsychotics and pituitary neoplasms in the WHO database. Psychopharmacol Bull. 2007;40(1):74-76.  
24 Ali S, Miller KK, Freudenreich O. Management of psychosis associated with a prolactinoma: case report and review of the literature. Psychosomatics. 2010;51(5):370-376.  
25 Bostwick JR, Guthrie SK, Ellingrod VL. Antipsychotic‐induced hyperprolactinemia. Pharmacotherapy. 2009;29(1):64-73.  
26 Rosenbloom AL. Hyperprolactinemia with antipsychotic drugs in children and adolescents. Int J Pediatr Endocrinol. 2010;2010(1):159402.