Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs between antidepressants. This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes.

A PRISMA-compliant systematic search of Web of Science and PubMed databases was performed from inception until Jan 5, 2023, for original studies reporting incidences or risks of hypoNa in adults using antidepressants. We modelled random-effects meta-analyses to compute overall event rates and odds ratios of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa event rates. We conducted subgroup analyses for geriatric populations and sodium cut-off value. The study is registered with PROSPERO, CRD42021269801.

We included 39 studies (n = 8,175,111). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (95%CI 1.911-5.225)). The highest event rates were found for SNRIs (7.44%), SSRIs (5.59%), and TCAs (2.66%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). Compared to SSRIs, SNRIs were significantly more likely (k = 10, OR = 1.292 (1.120 – 1.491), p < 0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 – 0.957), p = 0.032) to be associated with hypoNa.

Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

Oxcarbazepine (OXC) is an antiepileptic drug used as a mood stabilizer in patients diagnosed with bipolar disorder (BD). OXC has been reported as a source of hyponatremia in its use in both epilepsy and BD.

We present the case of a 53 year-old male patient diagnosed with Schizoaffective disorder, bipolar type who developed hyponatremia during his treatment with OXC.

The patient’s treatment was desvelafaxine 100 mg, Paliperidone depot 150 mg, Oxcarbazepine 600 mg which he had maintained for at least one year. He began to manifest headache, asthenia and mild confusion gradually, with morning predominance, without being clearly suggestive of an acute worsening.

In control analysis, the existence of sodium leveles of 127 and low osmolarity was observed. Therefore it was decided to suspend furosemide, close monitoring of water intake in order to rule out primary polydipsia and extra salt was introduced into the diet. Given the persistence of the symptoms, laboratory abnormalities and ruled out the existence of primary polydipsia, it was decided to suspend treatment with oxcarbazepine. After the discontinuation of the aforementioned drug the analytical findings went back to normal ranges and the symptoms disappeared.

Carrying out control tests in patients with psychiatric pathology and multiple psychiatric treatments is essential to be able to rule out analytical alterations which could be asymptomatic or with nonspecific symptoms that could be attributed to the underlying pathology. The easy reversal of symptoms encourages us to emphasize the study and differential diagnosis of each case.

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Hyponatremia is an electrolyte disorder that can be caused by multiple factors, among which the syndrome of inappropriate antidiuretic hormone secretion (SIAHS) is one of the most frequent causes. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressant drugs in all age groups for efficacy, safety, and adverse effects, although they can cause serious and undesirable side effects.

Report of a series of cases of patients with SIAHS secondary to the use of SSRIs.

We report 21 cases of patients between 52 and 76 years of age, of both sexes, undergoing treatment for depressive disorder with SSRI antidepressants and anxiolytics, concomitant with other clinical treatments (ACEI, thiazides, and carbamazepine). Biochemical laboratory and electrocardiogram studies were performed prior to the start of treatment.

In the first weeks (mean = 2.5) after starting psychopharmacological treatment, hyponatremia (mean = 126 mEq/L) was recorded in 9 symptomatic patients, and Inadequate Antidiuretic Hormone Secretion Syndrome (SIAHS) was diagnosed with referral to Nephrology and Endocrinology. The SSRI was withdrawn, achieving normalization of the biochemical values (plasma and urinary sodium, plasma, and urinary osmolarity), psychotherapy was reinforced until the rotation of another antidepressant. The mean time of suspension of the antidepressant was 7.1 days, the time of disappearance of symptoms after the suspension was 4.3 days and the normalization of biochemical values was 21.68 days. Only one case was severe and 5 required hospitalization.

In the cases presented, the SSRI antidepressants were associated with hyponatremia caused by the syndrome of inappropriate antidiuretic hormone secretion. This adverse event was more significant in elderly patients and in those treated with other drugs that cause the disease, such as antineoplastic, diuretic, and antiepileptic drugs, due to synergism between the causative mechanisms.

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Oxcarbazepine (OXC) is an antiepileptic drug widely used in the treatment of bipolar disorder (BD), specially when there are side effects with other mood stabilizers. Nevertheless, it isn’t innocuous of adverse effects and its consequences can even endanger the patient’s life.

Brief review of the literature on OXC-induced hyponatremia and exposure of a case report.

Review of the literature through research in the PubMed database, using the following keywords: “oxcarbazepine”, “hyponatremia” and “adverse effects”.

Although most of the patients are asymptomatic, hyponatremia is one of the most important side effects of OXC. About 29.9% of the patients develop hyponatremia, but only 2.5-3% of psychiatric patients develop severe hyponatremia. The risk of hyponatremia is higher during the first three months of treatment. Severe and/or symptomatic hyponatremia has important clinical implications and may be associated with neurological damage, including seizures, brain stem herniation and death. A 44-year-old woman diagnosed with BD started OXC due to drug intoxications with other mood stabilizers. Six days after initiating treatment, she presented persistent vomiting and severe hyponatremia was detected in blood tests. OXC was suspended with symptomatic resolution.

Healthcare professionals should be alert to symptoms that may arise in patients under OXC. Periodic evaluations of serum sodium levels should be carried out. Cases of severe and/or symptomatic hyponatremia should be rapidly identified and treated in order to reduce the risk of developing brain injury and death.

Psychogenic Polydipsia is defined as the desire to drink liquid in big quantities with an inappropriate activation of the mechanisms of thirst without loss of liquid for urine. This disorder is frequent enough and can derive in a water poisoning, a clinical presentation of high mortality.

Review of the Psychogenic Polydipsia in patients with schizophrenia and theoretical discussion of a case report.

A case report of a 58-year-old male, admitted in hospital with a clinical presentation of hyponatremia with severe low serum osmolarity secondary to Psychogenic Polydipsia. As psychiatric history he has a diagnosis of Paranoid Schizophrenia for forty years in treatment with Paliperidone 6 mg: 1-0-0, Haloperidol 10 mg: 0-0-0.5, Quetiapina 300 mg: 0-0-1, Trazodona 100 mg: 0-0-1, Ketazolam 30 mg: 0-0-1, Diazepam 10 mg: 0-0-1.

Psychogenic Polydipsia is not included in any section of current psychiatric classifications as specific diagnosis. There are several psychiatric disorders that may present with psychogenic polydipsia; however, the most common cause appears to be schizophrenia.

Mechanisms of hyponatremia in patients with schizophrenia are not well clarified; nevertheless, dopamine seems to be the common link between psychogenic polydipsia and schizophrenia.

The authors have not supplied their declaration of competing interest.