Effects of paroxetine combined with low-dose quetiapine on stress response and endocrine function in patients with treatment-resistant depression and sleep disorders.
Zhu Z & Lu M • Pakistan journal of pharmaceutical sciences • 2026
Paroxetine combined with a low dose of quetiapine is a clinically effective approach for treatment-resistant depression with sleep disorders, demonstrating superior efficacy over paroxetine alone in depression/anxiety scores, sleep quality, stress response, and endocrine function.
Key Findings
Results
The combination of paroxetine and low-dose quetiapine demonstrated superior clinical efficacy compared to paroxetine alone in patients with treatment-resistant depression and sleep disorders.
120 patients with treatment-resistant depression complicated by sleep disorders were divided into a control group (paroxetine alone) and a research group (paroxetine + low-dose quetiapine)
Clinical efficacy was assessed using the Hamilton Depression Scale (HAMD-17)
The research group demonstrated superior efficacy compared to the control group
The difference in clinical efficacy between groups was statistically significant (P<0.05)
Results
Patients receiving the combination therapy showed lower self-rating anxiety and depression scale scores after treatment compared to the control group.
Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were used to measure outcomes
The research group showed lower SAS/SDS scores than the control group after treatment
The difference was statistically significant (P<0.05)
Both anxiety and depression symptom measures favored the combination treatment group
Results
Sleep quality improved more significantly in the combination therapy group compared to the paroxetine-only group.
Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI)
The PSQI of the research group decreased more significantly compared to the control group after treatment
The difference was statistically significant (P<0.05)
Lower PSQI scores indicate better sleep quality
Results
The combination therapy group showed better stress injury alleviation compared to the control group.
Stress response was assessed via serum indexes including cortisol and epinephrine
The research group demonstrated better stress injury alleviation than the control group
The difference was statistically significant (P<0.05)
Cortisol and epinephrine levels were among the biomarkers used to assess stress response
Results
Endocrine function improved more in the combination therapy group than in the paroxetine-only control group.
Endocrine function was assessed using serum indexes including thyroid hormone levels
Better endocrine function improvement was determined in the research group compared to the control group
The difference was statistically significant (P<0.05)
Thyroid hormone was among the endocrine markers measured
Results
Treatment compliance and adverse reactions did not differ significantly between the combination therapy group and the paroxetine-only group.
Both treatment compliance and adverse reactions were compared between the two groups
The two groups were not statistically different in treatment compliance (P>0.05)
The two groups were not statistically different in adverse reactions (P>0.05)
This suggests the addition of low-dose quetiapine did not increase side effects or reduce compliance
What This Means
This research suggests that adding a low dose of quetiapine (an antipsychotic medication) to paroxetine (an antidepressant) produces better outcomes than paroxetine alone for people who have depression that hasn't responded to standard treatments and who also have sleep problems. The study enrolled 120 such patients and split them into two groups, comparing outcomes on standardized scales for depression, anxiety, and sleep quality, as well as biological markers in the blood related to stress hormones and thyroid function. Across all of these measures, patients receiving the combination treatment fared better than those receiving paroxetine alone.
Importantly, the combination treatment did not appear to cause more side effects or make patients less likely to stick with their treatment compared to paroxetine alone. This suggests the addition of low-dose quetiapine offers clinical benefits without an obvious increase in risk or burden to patients. The stress hormones cortisol and epinephrine, as well as thyroid hormone levels, all showed greater improvement in the combination therapy group, pointing to broader biological benefits beyond just mood and sleep.
This research suggests that for patients whose depression has not responded to standard antidepressant treatment and who also struggle with sleep, combining paroxetine with a low dose of quetiapine may be a more effective therapeutic strategy. The authors recommend this combination for clinical use based on their findings, though as with all psychiatric treatment decisions, individual patient circumstances and physician guidance would be important considerations.
Zhu Z, Lu M. (2026). Effects of paroxetine combined with low-dose quetiapine on stress response and endocrine function in patients with treatment-resistant depression and sleep disorders.. Pakistan journal of pharmaceutical sciences. https://doi.org/10.36721/PJPS.2026.39.4.REG.13681.1