Can SSRIs Cause Diabetes Insipidus?
SSRIs can rarely cause diabetes insipidus, though this is an extremely uncommon adverse effect with limited documentation in the medical literature.
Evidence for SSRI-Induced Diabetes Insipidus
The association between SSRIs and diabetes insipidus is poorly established in clinical guidelines and research:
A single case report documents sertraline overdose (20 tablets of 50 mg each) causing diabetes insipidus in a 17-year-old female patient, with symptoms effectively relieved by pituitrin treatment 1. This represents an acute overdose scenario rather than therapeutic dosing.
The World Health Organization's adverse effect database identified only 10 reports of clozapine-associated diabetes insipidus among 359 total drug-induced cases, with no specific mention of SSRIs as a class 2. Lithium dominated with 159 reports, followed by foscarnet with 15 reports 2.
Drug-induced diabetes insipidus is always nephrogenic (renal unresponsiveness to antidiuretic hormone) rather than central in origin 2.
Common SSRI Side Effects (Not Including Diabetes Insipidus)
The well-established adverse effects of SSRIs documented in guidelines include 3:
- Sweating (dose-related and commonly reported)
- Diarrhea, dizziness, dry mouth, fatigue, headache
- Sexual dysfunction
- Tremor and weight gain
- Gastrointestinal disturbances
These side effects are "commonly mild and short lived," though they cause 10-20% of patients to discontinue treatment 3.
Clinical Implications
Diabetes insipidus should not be considered a typical or expected adverse effect of SSRI therapy at therapeutic doses 4.
If polyuria (urine output exceeding 3 liters per day) develops in a patient taking an SSRI, investigate other causes first, including lithium co-administration (which causes nephrogenic diabetes insipidus in approximately 10% of long-term users), other nephrotoxic medications, or underlying medical conditions 2.
The diagnosis of drug-induced diabetes insipidus requires demonstration of renal unresponsiveness through a water deprivation test or desmopressin administration 5, 2.
Monitoring Recommendations
For patients on SSRIs experiencing unexplained polyuria:
- Measure urinary concentrating capacity during a 12-hour thirst test 2
- Assess response to desmopressin to differentiate central from nephrogenic causes 5
- Review all concurrent medications, particularly lithium, foscarnet, antimicrobials, and cytostatics 2
- Monitor electrolytes to prevent dehydration and associated complications 6