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Antipsychotic-induced hyperprolactinemia: synthesis of world-wide guidelines and integrated recommendations for assessment, management and future research

Abstract

Rationale

Hyperprolactinemia is a highly prevalent adverse effect of many antipsychotic agents, with potentially serious health consequences. Several guidelines have been developed for the management of this condition; yet, their concordance has not been evaluated.

Objectives

The objectives of this paper were (1) to review current clinical guidelines; (2) to review key systematic evidence for management; and (3) based on our findings, to develop an integrated management recommendation specific to male and female patients who are otherwise clinically stabilised on antipsychotics.

Methods

We performed searches of Medline and EMBASE, supplemented with guideline-specific database and general web searches, to identify clinical guidelines containing specific recommendations for antipsychotic-induced hyperprolactinemia, produced/updated 01/01/2010–15/09/2016. A separate systematic search was performed to identify emerging management approaches described in reviews and meta-analyses published ≥ 2010.

Results

There is some consensus among guidelines relating to baseline PRL screening (8/12 guidelines), screening for differential diagnosis (7/12) and discontinuing/switching PRL-raising agent (7/12). Guidelines otherwise diverge substantially regarding most aspects of screening, monitoring and management (e.g. treatment with dopamine agonists). There is an omission of clear sex-specific recommendations. Systematic literature on management approaches is promising; more research is needed. An integrated management recommendation is presented to guide sex-specific clinical response to antipsychotic-induced hyperprolactinemia. Key aspects include asymptomatic hyperprolactinemia monitoring and fertility considerations with PRL normalisation.

Conclusion

Further empirical work is key to shaping robust guidelines for antipsychotic-induced hyperprolactinemia. The integrated management recommendation can assist clinician and patient decision-making, with the goal of balancing effective psychiatric treatment while minimising PRL-related adverse health effects in male and female patients.

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Correspondence to Jayashri Kulkarni.

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Source of support and declaration of interest

Jayashri Kulkarni has received an Independent Educational Grant from Janssen Cilag to support the production of this review of current clinical guidelines and emerging treatment methods to support updated recommendations for the management of antipsychotic-induced hyperprolactinemia.

Appendices

Appendix A Database(s): Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present

Search Strategy:

# Searches Results
1 Hyperprolactinemia/ 2961
2 hyperprolactin?emia.ti,ab. 5732
3 exp Antipsychotic Agents/ 113,542
4 antipsychotic*.ti,ab. 32,619
5 exp Practice Guideline/ 21,920
6 exp Guideline/ 28,500
7 exp Guideline Adherence/ 25,525
8 guideline*.ti,ab. 246,580
9 (clinical adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 47,048
10 (national adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 16,508
11 (department* adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 1390
12 (practice adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 31,665
13 (society adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 3594
14 (institut* adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 7426
15 (board adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 714
16 (association adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 3919
17 1 or 2 6483
18 3 or 4 124,034
19 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 313,469
20 17 and 18 and 19 20

Appendix B Database(s): Embase 1974 to 2016 September 12

Search Strategy:

# Searches Results
1 Hyperprolactinemia/ 9511
2 hyperprolactin?emia.ti,ab. 7334
3 exp Antipsychotic Agents/ 247,714
4 antipsychotic*.ti,ab. 47,616
5 guideline*.ti,ab. 362,228
6 (clinical adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 65,937
7 (national adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 24,506
8 (department* adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 2387
9 (practice adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 42,927
10 (society adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 5760
11 (institut* adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 11,518
12 (board adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 982
13 (association adj3 (guideline* or guidance or standard? or protocol*)).ti,ab. 5405
14 exp practice guideline/ 376,919
15 1 or 2 11,327
16 3 or 4 254,259
17 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 657,971
18 15 and 16 and 17 213

Appendix C Database(s): Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present

Search Strategy:

# Searches Results
1 Hyperprolactinemia/ 2978
2 hyperprolactin?emia.ti,ab. 5783
3 1 or 2 6536
4 Antipsychotic Agents/ 48,899
5 antipsychotic*.ti,ab. 33,007
6 4 or 5 61,385
7 systematic review.ti,ab. 82,990
8 meta-analysis/ 74,565
9 meta-analysis.ti,ab. 88,655
10 7 or 8 or 9 161,893
11 3 and 6 and 10 28

Appendix D Database(s): Embase 1974 to 2016 October 19

Search Strategy:

# Searches Results
1 Hyperprolactinemia/ 9849
2 hyperprolactin?emia.ti,ab. 7402
3 1 or 2 11,470
4 Antipsychotic Agents/ 65,495
5 antipsychotic*.ti,ab. 47,989
6 4 or 5 90,337
7 systematic review.ti,ab. 100,240
8 meta-analysis/ 150,109
9 meta-analysis.ti,ab. 111,353
10 7 or 8 or 9 221,508
11 3 and 6 and 10 120

Appendix E Database(s): EBM Reviews - Cochrane Database of Systematic Reviews 2005 to October 19, 2016

Search Strategy:

# Searches Results
1 [Hyperprolactinemia/] 0
2 hyperprolactin?emia.ti,ab. 4
3 1 or 2 4
4 [Antipsychotic Agents/] 0
5 antipsychotic*.ti,ab. 182
6 4 or 5 182
7 3 and 6 2

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Grigg, J., Worsley, R., Thew, C. et al. Antipsychotic-induced hyperprolactinemia: synthesis of world-wide guidelines and integrated recommendations for assessment, management and future research. Psychopharmacology 234, 3279–3297 (2017). https://doi.org/10.1007/s00213-017-4730-6

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Keywords

  • Hyperprolactinemia
  • Antipsychotic
  • Prolactin
  • Psychiatric treatment
  • Clinical guidelines