Does Invega Sustenna (paliperidone) increase prolactin levels?

Does Invega Sustenna Increase Prolactin Levels?

Yes, Invega Sustenna (paliperidone palmitate) consistently and significantly increases prolactin levels in both men and women, with elevations ranging from 1500 to 3996 mIU/L (normal upper limit 500 mIU/L), and approximately 39% of patients develop hyperprolactinemia during treatment. 1, 2

Magnitude and Frequency of Prolactin Elevation

Paliperidone palmitate causes substantial prolactin increases across all patient populations:

• In clinical trials with 2,831 patients who had recorded prolactin levels, 38.8% developed elevated prolactin at some point during treatment (39.5% of males and 37.7% of females) 2
• The elevation is dose-independent, with no significant correlation between monthly dose and the proportion of patients with elevated prolactin (p = 0.109) 2
• Prolactin levels can reach 1500-3996 mIU/L, which is 3-8 times the normal upper limit of 500 mIU/L 1
• These elevations typically occur within 3 weeks to 4 months after starting treatment 1

Clinical Manifestations and Symptomatic Rates

Most patients with elevated prolactin remain asymptomatic, but clinically significant effects do occur:

• Only 2.0% of all patients develop symptomatic prolactin-related adverse events, despite the 38.8% rate of biochemical hyperprolactinemia 2
• Among 115 prolactin-related adverse events documented, 51 (44.3%) represented asymptomatic hyperprolactinemia 2
• The remaining 64 symptomatic events included galactorrhea (the most distressing symptom reported), menstrual disturbances, and sexual dysfunction 1, 3
• Only 0.41% of patients (4.7 events per 1000 patients) required specific treatment for prolactin-related adverse effects 2

Comparison with Other Antipsychotics

Paliperidone palmitate and risperidone long-acting injection are among the highest-risk second-generation antipsychotics for hyperprolactinemia:

• First-generation antipsychotics pose the greatest overall risk, but among second-generation agents, risperidone and paliperidone most frequently increase prolactin secretion 3
• When switching from risperidone long-acting injection to paliperidone palmitate, male patients showed significant reductions in prolactin levels at 1,3, and 6 months, while female patients and males switched from oral paliperidone showed no significant changes 4
• In head-to-head trials comparing paliperidone palmitate (mean doses 70-110 mg every 4 weeks) with risperidone long-acting injection (mean doses ~35 mg every 2 weeks), both caused substantial prolactin increases with no significant difference between them 5

Long-Term Consequences and Quality of Life Impact

Hyperprolactinemia carries both short-term and long-term health risks that affect morbidity and quality of life:

• Short-term effects: Menstrual disturbances, galactorrhea, sexual dysfunction, gynecomastia, and infertility 3
• Long-term effects: Decreased bone mineral density and potential increased risk of breast cancer (though the latter requires further study) 3
• Two of four patients in one case series experienced galactorrhea, described as a "distressing adverse effect" that significantly impacted subsequent treatment management and the therapeutic relationship 1

Monitoring and Management Algorithm

Given the high frequency but low symptomatic rate, implement the following approach:

1. Baseline assessment: Measure prolactin levels before initiating paliperidone palmitate to establish a reference point 2, 3

2. Periodic monitoring: Assess patients at 1,3, and 6 months after initiation, then every 6-12 months during maintenance treatment 2, 4

3. Clinical assessment at each visit: Specifically inquire about menstrual irregularities, galactorrhea, sexual dysfunction, and gynecomastia, as many patients may not volunteer these symptoms 1, 3

4. If asymptomatic hyperprolactinemia develops: Continue current treatment with ongoing monitoring, as most patients remain asymptomatic and do not require intervention 2

5. If symptomatic hyperprolactinemia develops: Consider three options in order of preference:

   • Switch to an antipsychotic with lower prolactin risk (aripiprazole, quetiapine, clozapine) 3
   • Reduce the dose to the lowest effective level 3
   • Add a dopamine agonist (cabergoline preferred over bromocriptine for better tolerability), though this may compromise antipsychotic efficacy 3, 6

Critical Pitfalls to Avoid

• Do not assume asymptomatic patients are unaffected: Even without symptoms, chronic hyperprolactinemia can cause bone density loss and other long-term complications 3
• Do not overlook the impact on treatment adherence: Distressing symptoms like galactorrhea can disrupt the therapeutic relationship and lead to medication discontinuation 1
• Do not forget sex-specific effects: While overall rates are similar between sexes, the clinical manifestations differ (galactorrhea and menstrual changes in women; gynecomastia and sexual dysfunction in men) 2, 3
• Do not rely solely on laboratory values: Two patients in one series had significantly elevated prolactin (1500-3996 mIU/L) but remained completely asymptomatic, while others with similar elevations experienced distressing symptoms 1