Pregnenolone for Schizophrenia: Does It Help?

randomized-controlled-trial PMID: 25030803

Quick Summary: A study looked at whether pregnenolone could help people with schizophrenia. The results showed that pregnenolone might improve daily functioning, like communication, but didn't significantly help with thinking problems.

What The Research Found

Researchers found that taking pregnenolone for 8 weeks improved the ability of people with schizophrenia to function in their daily lives. This included better communication skills. However, pregnenolone didn't seem to improve thinking skills, like memory or focus, in this study.

Study Details

Who was studied: 120 adults with schizophrenia.

How long: The study lasted for 8 weeks.

What they took: Half the participants took pregnenolone (50mg daily), and the other half took a placebo (a sugar pill).

What This Means For You

This research suggests that pregnenolone might help people with schizophrenia manage their daily lives better. This could mean improvements in things like work, social interactions, or self-care. However, it's important to remember:

Talk to your doctor: Don't start taking pregnenolone without talking to your doctor first.

Not a cure: Pregnenolone may not address all symptoms of schizophrenia.

More research needed: This was a single study, and more research is needed to confirm these findings and understand how pregnenolone works.

Study Limitations

Small study: The study was relatively small, so the results may not apply to everyone.

Short duration: The study only lasted 8 weeks. Longer studies might show different results.

Focus on function, not thinking: The study didn't find improvements in thinking skills.

Specific population: The study was conducted in Singapore, so the results may not be the same for people in other places.

Key Findings

This 8-week randomized controlled trial found that adjunctive pregnenolone (50 mg/day) did not significantly improve cognitive symptoms (as measured by the MATRICS Consensus Cognitive Battery) in schizophrenia patients. However, pregnenolone demonstrated statistically significant improvements in functional capacity (UCSD Performance-based Skills Assessment-Brief composite scores, p = 0.03) and communication skills (p < 0.001) compared to placebo. Serum pregnenolone levels correlated with functional improvements in females (r_s = 0.497, p < 0.042) but not males. Negative symptoms (Scale for Assessment of Negative Symptoms) were not improved, likely due to low baseline severity. Pregnenolone was well-tolerated.

Study Design

A double-blind, placebo-controlled randomized controlled trial conducted at the Institute for Mental Health in Singapore. After a placebo lead-in phase, 120 participants with schizophrenia were randomized to pregnenolone (n = 56) or placebo (n = 55). A modified intent-to-treat analysis was used. Primary endpoints were changes in cognitive symptoms (MCCB), functional capacity (UPSA-B), and negative symptoms (SANS) at 8 weeks.

Dosage & Administration

Participants received 50 mg of pregnenolone orally once daily as a capsule formulation. Compliance was monitored via pill counts and serum level measurements.

Results & Efficacy

Cognitive Symptoms: No significant difference in MCCB composite scores between groups (p not reported*).
Functional Capacity: Pregnenolone improved UPSA-B composite scores (p = 0.03) and communication subscale scores (p < 0.001).
Negative Symptoms: Minimal baseline SANS scores (mean ~15.5) limited detectable improvement.
Gender Subgroup: In females (n = 17), higher post-treatment serum pregnenolone correlated with greater UPSA-B improvement (r_s = 0.497, p < 0.042).
Safety: No serious adverse events; pregnenolone was well-tolerated.

Limitations

Baseline Ceiling Effect: Participants had mild negative symptoms at baseline, reducing sensitivity to detect SANS improvements.
Short Duration: 8 weeks may be insufficient to observe cognitive or neurosteroid-related effects.
Subgroup Analysis: Female-specific findings (n = 17) require replication due to small sample size.
Single Site: Conducted in Singapore; results may not generalize to other populations.
Mechanistic Gaps: Neurosteroid metabolites (e.g., allopregnanolone) were not directly measured to confirm proposed mechanisms.

Clinical Relevance

This study suggests pregnenolone (50 mg/day) may enhance functional capacity in schizophrenia patients, particularly communication skills, without improving cognitive deficits or negative symptoms. The gender-specific correlation in females hints at potential individual variability in response, warranting further research. While promising, these results should be interpreted cautiously due to the small sample size for subgroup analyses and short duration. Pregnenolone appears safe as an adjunctive therapy, but larger trials are needed to validate its role in schizophrenia treatment. Users should consult healthcare providers before use, as effects on cognition were absent and mechanisms remain incompletely understood.

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