Background: Lithium is a cornerstone in the treatment of bipolar disorder (BD). However, lithium use requires careful monitoring of thyroid function due to associated dysfunctions. The aim of our real-world study is to retrospectively evaluate the impact of lithium on thyroid function and how these thyroid alterations can be measured and managed. Methods: A retrospective observational study was performed on 150 patients with BD who started lithium treatment at the University Hospital of Siena. Thyroid function was assessed at baseline and after the introduction of lithium by measuring TSH, T3, and T4 levels at baseline and after 3, 6, 9, and 12 months, during which changes in psychiatric symptoms were also evaluated using specific psychometric scales. Results: Significant increases in TSH levels were observed at 3 and 6 months, while T3 and T4 levels decreased significantly at 3 months. Transient thyroid dysfunction occurred in 36.7% of patients, but normalized without the discontinuation of lithium or need for thyroid replacement therapy in most cases; however, replacement therapy was initiated in 8.7% of patients. There were no significant differences in treatment response between patients with and without thyroid abnormalities, as the abnormalities were transient or resolved. Conclusions: In our sample, lithium induced some cases of hypothyroidism, which, being transient or corrected with replacement therapy, did not interfere with symptomatic improvement. These findings underscore the necessity for continuous thyroid function monitoring during lithium therapy. Clinicians should be prepared to initiate thyroid replacement therapy, when necessary, as timely management can prevent the interruption of lithium treatment and ensure ongoing symptomatic improvement in BD patients. Future studies could include larger and more diverse populations to validate these findings further, extending the follow-up period beyond 12 months to better observe long-term thyroid function trends and management outcomes.

Lithium is a key medication for the treatment of psychiatric disorders and is also used in various industrial applications (including battery production and recycling). Here, we review published data on the endocrine-disrupting potential of lithium, with a particular focus on the thyroid hormone system. To this end, we used PubMed and Scopus databases to search for, select and review primary research addressing human and animal health endpoints during or after lithium exposure at non-teratogenic doses. Given the key role of thyroid hormones in neurodevelopmental processes, we focused at studies of the neural effects of developmental exposure to lithium in humans and animals. Our results show that lithium meets the World Health Organization's definition of a thyroid hormone system disruptor - particularly when used at therapeutic doses. When combined with knowledge of adverse outcome pathways linking molecular initiating events targeting thyroid function and neurodevelopmental outcomes, the neurodevelopmental data reported in animal experiments prompt us to suggest that lithium influences neurodevelopment. However, we cannot rule out the involvement of additional modes of action (i.e. unrelated to the thyroid hormone system) in the described neural effects. Given the increasing use of lithium salts in new technologies, attention must be paid to this emerging pollutant - particularly with regard to its potential effects at environmental doses on the thyroid hormone system and potential consequences on the developing nervous system.

Lithium carbonate is used to manage various mood disorders, but it can cause thyroid abnormalities, including goiter, hypothyroidism, and hyperthyroidism. In rare cases, it can lead to giant goiter and subclinical hyperthyroidism, which may require surgical intervention in severe cases.

This case represents a rare development of giant goiter and subclinical hyperthyroidism in a schizophrenia patient who was subjected to prolonged lithium carbonate treatment. The enlarged thyroid gland caused pressure on the airway and recurrent laryngeal nerve, which led to respiratory distress, hoarseness, and dysphagia. The immediate danger of suffocation required urgent surgical intervention. In this report, we describe the case of a 41-year-old Chinese woman. This sheds light on the etiology and challenges associated with managing a giant goiter. The patient underwent a subtotal thyroidectomy to relieve airway compression and facilitate airway expansion. Prior to the procedure, the patient was given iodine to prepare. Concurrently, changes were made to the psychiatric medication regimen. Following surgery, the patient's respiratory function and vocal cord functionality improved significantly, and her mental state remained stable.

It is essential to monitor thyroid function, test thyroid antibody levels, and perform thyroid ultrasounds consistently in all patients undergoing long-term lithium carbonate treatment. This vigilance helps prevent severe and potentially life-threatening thyroid enlargement.

Low doses of lithium, as might be used for mood or dementia prevention, do not carry the same renal, toxicity, and tolerability problems of doses used for prophylaxis or treatment of mania. However, thyroid effects of low doses have not been investigated. Our goal in this study was to assess the changes in thyroid-stimulating hormone (TSH) associated with a broad range of lithium levels, including those well below the therapeutic range for bipolar disorders.

This study was conducted in a small healthcare system with 19 associated primary care clinics served by a Collaborative Care program of psychiatric consultation. In this retrospective review of electronic records, we searched for patients who had received a lithium prescription and both pre- and post-lithium thyroid-stimulating hormone (TSH) levels.

Patients with low lithium levels (<0.5 mEq/L, N = 197) had a mean thyroid-stimulating hormone (TSH) increase of 0.52 mIU/L. Patients with maintenance lithium levels (0.5-0.8 mEq/L; N = 123) had a mean TSH increase of 1.01 mIU/L; and patients with antimanic lithium levels (>0.8 mEq/L; N = 79) had a mean TSH increase of 2.16 mIU/L. The probability of TSH exceeding the upper limit of normal in our laboratory (>4.2 mIU/L) was positively associated with pre-lithium TSH.

These results suggest that the risk of lithium-induced hypothyroidism is dose-related, and relatively small with very low doses, but thyroid monitoring, including a pre-lithium TSH, is still warranted.

Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders.

Hypothyroxinaemia might be easily ignored, because attention is typically paid to individuals with elevated thyroid stimulating hormone (TSH). In this study, we aimed to evaluate the association of oxcarbazepine use as adjuvant for treatment of schizophrenia with hypothyroxinaemia and central set point of thyroid homeostasis.

This retrospective cohort study was conducted in the Second Affiliated Hospital of Xinxiang Medical University. Inpatients with a diagnosis of schizophrenia admitted between January 2016 and October 2019 with normal thyroid function at admission were included. Oxcarbazepine use was the exposure measure. Newly developed hypothyroxinaemia was the primary outcome measure and parameters of thyroid homeostasis central set point as measured by TSH index and thyroid feedback quantile-based index (TFQI) were the secondary outcome measures.

In total, 1207 eligible patients were included. The occurrence of hypothyroxinaemia in patients who received oxcarbazepine was higher (35/107, 32.7%) than in those patients who did not (152/1099, 13.8%), with adjusted relative risk of 2.24 and 95% confidence interval of 1.57 and 3.17. Oxcarbazepine use was associated with greater reduction in TSH index (adjusted β -0.33 and 95% confidence interval -0.48, -0.19) and TFQI (adjusted β -0.24 and 95% confidence interval -0.31, -0.16).

Oxcarbazepine use was independently associated with increased risk of developing hypothyroxinaemia, and greater reduction in TSH index and TFQI, suggesting that impaired central set point of thyroid homeostasis might be involved in the mechanism of oxcarbazepine-induced hypothyroxinaemia.

To assess the association between acute phase treatment by valproate as an adjunctive drug and risk of new onset hypothyroidism in a large cohort of patients affected by schizophrenia.

We conducted a retrospective cohort study in a psychiatric hospital in China between January 2016 and December 2018. We obtained approval from the Ethics Committee of the study hospital prior to the commencement of the study. Patients who were diagnosed with schizophrenia and admitted to the study hospital during the study period with thyroid function tests at admission and during hospitalization were included. Patients with abnormal thyroid function at admission were excluded. Hypothyroidism, defined as TSH>4.2 mU/L or on L-thyroxine treatment, was the primary outcome. The primary exposure was adjunctive valproate plus atypical antipsychotics (AAPD), the secondary exposure was lithium plus AAPD and the comparison group was AAPD only. Adjusted relative risk (RR) and 95% confidence interval (CI) were estimated by log-binomial model to assess the independent association between valproate treatment and risk of hypothyroidism.

A total of 1622 eligible patients were included the final analysis. Rate of new onset hypothyroidism was 10.7% and 20.9% in AAPD only and valproate plus AAPD groups, respectively. Adjusted RR (95% CI) for valproate plus AAPD was 1.85 (1.44-2.38), with AAPD only group as reference. Similarly, adjusted RR (95% CI) for lithium plus AAPD was 1.93 (1.32-2.69).

Similar with lithium, valproate as adjunctive drug is associated with increased risk of new onset hypothyroidism during acute phase treatment for schizophrenia.

Thyroid abnormalities are documented consequences of quetiapine treatment. This may have clinical implications as changes in thyroid hormones may deteriorate a person's affective state. Yet less is known about the clinical factors and underlying mechanisms associated with thyroid hormones on quetiapine therapy. We therefore systematically reviewed the published literature of evidence of quetiapine-induced thyroid abnormalities. We searched MEDLINE, PsycINFO, Google Scholar, and EMBASE for articles in which individuals developed biochemically confirmed thyroid abnormalities (with or without clinical symptoms) while on quetiapine treatment. We included case reports, case series, observational, and experimental studies. We included 32 studies, 20 of which were observational and experimental studies. There were 10 case reports and 1 case series. All the research designs suggested an association between quetiapine and hypothyroidism. However, these findings were limited by the quality of the included studies and the general lack of either a clear temporal relationship or dose response. Quetiapine has been associated with thyroid abnormalities, mainly with hypothyroidism. Drug imputability in these abnormalities is not always clear, and the underlying pathophysiology may include immunological and nonimmunological mechanisms. Large prospective studies are required to clarify this association and to further inform the management of patients treated with quetiapine where hypothyroidism occurs.

Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made.

A systematic literature search identified current treatment guidelines for depression published in English. Guidelines were quality assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Data relating to the prescription of pharmacological augmenters were extracted from those developed with sufficient rigor, and the included recommendations compared.

Total of 1696 records were identified, 19 guidelines were assessed for quality, and 10 were included. Guidelines differed in their quality, the stage at which augmentation was recommended, the agents included, and the evidence base cited. Lithium and atypical antipsychotics were recommended by all 10, though the specific advice was not consistent. Of the 15 augmenters identified, no others were universally recommended.

This review provides a comprehensive overview of current pharmacological augmentation recommendations for major depression and will support clinicians in selecting appropriate treatment guidance. Although some variation can be accounted for by date of guideline publication, and limited evidence from clinical trials, there is a clear need for greater consistency across guidelines to ensure patients receive consistent evidence-based care.

The association between lithium and thyroid dysfunction has long been known. However, it remains unknown if lithium-associated hypothyroidism is reversible once lithium treatment has been stopped.

To determine whether lithium-associated hypothyroidism was reversible in patients who subsequently discontinued lithium.

A retrospective cohort study in the Swedish region of Norrbotten into the effects and side- effects of lithium treatment and other drugs for relapse prevention (Lithium - Study into Effects and Side Effects). For this particular study, we reviewed medical records between 1997 and 2015 of patients with lithium-associated hypothyroidism who had discontinued lithium.

Of 1340 patients screened, 90 were included. Of these, 27% had overt hypothyroidism at the start of thyroid replacement therapy. The mean delay from starting lithium to starting thyroid replacement therapy was 2.3 years (SD 4.7). In total, 50% of patients received thyroid replacement therapy within 10 months of starting lithium. Of 85 patients available for follow-up, 41% stopped thyroid replacement therapy after lithium discontinuation. Only six patients reinstated thyroid replacement therapy subsequently. Of these, only one had overt hypothyroidism.

Lithium-associated hypothyroidism seems reversible in most patients once lithium has been discontinued. In such cases, thyroid replacement therapy discontinuation could be attempted much more often than currently done. Based on the limited evidence of our study, we can expect hypothyroidism to recur early after thyroid replacement therapy discontinuation, if at all.

Conclusions regarding the association between antithyroid antibodies or thyroid dysfunction and rapid cycling bipolar disorder (RCBD) have been conflicting. Previous studies suggest that the impact of antithyroid antibodies on mental wellbeing seems to be independent of thyroid function. Here, we investigated their independent association with RCBD in a large, well-defined population of bipolar disorder (BD).

Fast serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid Stimulating Hormone (TSH), TPO-abs and Tg-abs were simultaneously measured in 352 patients with BD. Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education.

Neither hypothyroidism nor hyperthyroidism was significantly associated with RCBD. Both TPO-abs and Tg-abs were significantly related to RCBD, even after controlling for gender, age, marriage status, education, antidepressants treatment, comorbidity of thyroid diseases, and thyroid function (serum levels of FT3, FT4 and TSH). Although TPO-abs and Tg-abs were highly correlated with each other, binary logistic regression with forward LR selected TPO-abs, instead of Tg-abs, to be associated with RCBD. TPO-abs was significantly, independently of Tg-abs, associated with hyperthyroidism, while Tg-abs was marginally significantly related to hypothyroidism at the presence of TPO-abs.

TPO-abs might be treated as a biomarker of RCBD. Further exploring the underlying mechanism might help understand the nature of RCBD and find out new treatment target for it.

Background: Epidemiological data reveal that treatment with lithium, a mood stabilizer, is associated with decreased incidence and mortality of certain cancer types, such as melanoma. Therefore, repositioning of lithium as an anticancer agent has emerged as a promising strategy in oncology. Since lithium affects the physiology of several endocrine tissues, the goal of this study was to analyze the role of lithium in the pathogenesis and treatment of tumors of the endocrine system. Methods: The databases of PubMed, EMBASE, MEDLINE, were searched from January 1970 through February 2019 for articles including the keywords "lithium and"-"thyroid cancer," "thyroid nodule," "parathyroid adenoma," "parathyroid carcinoma," "pituitary adenoma," "pituitary neuroendocrine tumor," "neuroendocrine tumor," "carcinoid," "adrenal adenoma," "adrenal carcinoma," "pheochromocytoma/paraganglioma." Preclinical in vitro and in vivo studies as well as case series, retrospective cohort studies and prospective trials were selected for the analysis. Results: Treatment with lithium has been associated with a higher prevalence of thyroid enlargement, hypothyroidism and increased calcium levels due to parathyroid adenoma or hyperplasia, as one of the mechanisms of its action is to stimulate proliferation of normal follicular thyroid and parathyroid cells via activation of the Wnt signaling pathway. Supratherapeutic concentrations of lithium decrease the activity of glycogen synthase kinase-3β (GSK-3β), leading to cell cycle arrest in several in vitro cancer models including medullary thyroid cancer (TC), pheochromocytoma/paraganglioma and carcinoid. Growth inhibitory effects of lithium in vivo have been documented in medullary TC xenograft mouse models. Clinically, lithium has been used as an adjuvant agent to therapy with radioactive iodine (RAI), as it increases the residence time of RAI in TC. Conclusion: Patients chronically treated with lithium need to be screened for hypothyroidism, goiter, and hyperparathyroidism, as the prevalence of these endocrine abnormalities is higher in lithium-treated patients than in the general population. The growth inhibitory effects of lithium in medullary TC, pheochromocytoma/paraganglioma and carcinoid were achieved with supratherapeutic concentrations of lithium thus limiting its translational perspective. Currently available clinical data on the efficacy of lithium in the therapy of endocrine tumors in human is limited and associated with conflicting results.

The aim of the study was to compare the structure and function of the thyroid in patients with bipolar disorder (BD) receiving long-term lithium treatment, with BD patients never receiving lithium.

Ninety-eight patients (68 female and 30 male), aged 62 ± 13 years, receiving lithium for 3-47 years (mean 19 ± 10 years), and 39 patients (27 female and 12 male), aged 57 ± 10 years, receiving other mood-stabilizing drugs but never treated with lithium, were included. The thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were estimated, and the ultrasonographic study of the thyroid gland was performed.

Compared with patients not receiving lithium, lithium-treated patients had significantly higher concentrations of TSH and fT4 and the lower concentration of fT3. However, the percentage of hypothyroidism was not different in both groups. Lithium-treated patients also had significantly higher thyroid volume, the higher number of focal changes >1 cm, and more frequent goiter. The structural changes were not related to the hormones' concentrations.

The results show a significant association between long-term lithium treatment and the increase of TSH and fT4, the decrease of fT3, higher thyroid volume, and more frequent goiter and nodular goiter. The effect of lithium on thyroid structure was not associated with its effect on thyroid hormones.

The prescribing of Lithium is common in psychiatric clinical practice. The aim of this study was to identify the most common endocrine side effects associated with this drug and to clarify the pathophysiological basis. A systematic review was conducted in Psycinfo, Embase, PubMed, and Scopus. A computerised search for information was performed using a PICO (patient, intervention, comparative, outcomes) strategy. The main neuroendocrine alterations were reported in kidneys, thyroid and parathyroid glands, pancreas, and the communication pathways between the pituitary and adrenal glands. The pathophysiological mechanisms are diverse, and include the inhibition of the thyroid adenylate cyclase sensitive to the thyroid stimulant hormone (TSH) sensitive adenylate cyclase, which causes hypothyroidism. It also reduces the expression of aquaporin type 2, which is associated with nephrogenic diabetes insipidus, and the loss of the ionic balance of calcium that induces hyperparathyroidism and hypercalcaemia. Other considerations are related to alterations in the hypothalamic-pituitary-adrenal axis and a decrease in the production of catecholamines. Finally, another side-effect is the glycaemic dysregulation caused by the insulin resistance. Periodical clinical and para-clinical evaluations are necessary. The author proposes an evaluation scheme.

Men and women often experience different symptoms or rates of occurrence for a variety of mood disorders. Many of the symptoms of mood disorders overlap with autoimmune disorders, which also have a higher prevalence in women. There is a growing interest in exploring the immune system to provide biomarkers for diagnosis of mood disorders, along with new targets for developing treatments. This review examines known sex differences in the immune system and their relationship to mood disorders. We focus on immune alterations associated with unipolar depression, bipolar depression, and anxiety disorders. We describe work from both basic and clinical research examining potential immune mechanisms thought to contribute to stress susceptibility and associated mood disorders. We propose that sex and age are important, intertwined factors that need to be included in future experimental designs if we are going to harness the power of the immune system to develop a new wave of treatments for mood disorders.

Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to supply a systematic overview of all scientific evidence pertaining to the acute and long-term treatment of bipolar mixed states in adults.

Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A-F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode.

Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention.

The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands.

Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept.

Recent observational studies have focused on lithium treatment in the elderly, with particular reference to safety in terms of thyroid and renal functions. The purpose of this study was to compare the clinical characteristics of patients starting lithium treatment before (N = 79) or after (N = 31) the age of 65 years. Patients were followed up for 6 years with focus on renal function and prescription of levothyroxine and methimazole.

At baseline, median lithium serum concentration was 0.55 mmol/l. The estimated glomerular filtration rate was lower than 60 ml/min/1.73 m² in 43 (39%) patients. In a multiple regression analysis controlling for age and gender, we found a significant effect of duration of lithium treatment on estimated glomerular filtration rate (-0.85 ml/min/1.73 m² per year of prior exposure). The annual decline during follow-up was 2.3 ml/min/1.73 m². Two patients were prescribed levothyroxine, and two were prescribed methimazole for the first time during follow-up.

Median lithium serum concentration in this cohort of elderly patients with mainly bipolar disorders was lower than the therapeutic range indicated for younger adults. The decline in glomerular filtration rate may be accelerated by long-term lithium use. Thyroid and renal functions continue to require close monitoring throughout the course of lithium treatment. Trial registration NP/2013/3836. Registered 24 June 2013.

Lithium has many effects on thyroid physiology. Although these side effects have been known for a long time, large sample studies of lithium-treated patients using ultrasonography are lacking. The aim of this study is to investigate the detailed thyroid morphologies, hormone levels, and antibodies of lithium-treated patients compared with healthy controls.

This cross-sectional study involved 84 lithium-treated patients with bipolar disorder and 65 gender and age similar controls who had never been exposed to lithium. Subjects between 18 and 65 years of age were eligible for the study. Venous blood samples were acquired to determine the levels of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid antibodies; also, ultrasonographic examinations of the patients' thyroid glands were performed.

There were no statistically significant differences in smoking habits, known thyroid disease, thyroid medication use, familial thyroid disease, fT4 level, autoimmunity, thyroid nodule presence, or Hashimoto's thyroiditis between the lithium and control groups. The median TSH level and thyroid volume were significantly higher in the lithium group. In the lithium group, 14 cases (16.7%) of hypothyroidism, seven cases (8.3%) of subclinical hypothyroidism, and one case (1.2%) of subclinical hyperthyroidism were defined; in the control group, seven cases (10.8%) of hypothyroidism and two cases (3.1%) of subclinical hyperthyroidism were defined. Thyroid dysfunction, goiter, parenchymal abnormality, ultrasonographically defined thyroid abnormality, and thyroid disorder were found to be more prevalent in the lithium group. 90% of patients with goiter and 74.3% of patients with ultrasonographic pathologies were euthyroid.

It is important to note that 90% of the patients with goiter were euthyroid. This indicates that monitoring by blood test alone is insufficient. The prevalence rates of 47.6% for goiter and 83.3% for ultrasonographic pathology demonstrate that ultasonographic follow-up may be useful in lithium-treated patients. To determine whether routine ultrasonographic examination is necessary, large sample prospective studies are necessary due to the limitations of this study.

Thyroid abnormalities in patients with bipolar disorder (BD) have been linked to lithium treatment for decades, yet other drugs have been less well studied. Our objective was to compare hypothyroidism risk for lithium versus the anticonvulsants and second-generation antipsychotics commonly prescribed for BD.

Administrative claims data on 24,574 patients with BD were analyzed with competing risk survival analysis. Inclusion criteria were (i) one year of no prior hypothyroid diagnosis nor BD drug treatment, (ii) followed by at least one thyroid test during BD monotherapy on lithium carbonate, mood-stabilizing anticonvulsants (lamotrigine, valproate, oxcarbazepine, or carbamazepine) or antipsychotics (aripiprazole, olanzapine, risperidone, or quetiapine). The outcome was cumulative incidence of hypothyroidism per drug, in the presence of the competing risk of ending monotherapy, adjusted for age, sex, physician visits, and thyroid tests.

Adjusting for covariates, the four-year cumulative risk of hypothyroidism for lithium (8.8%) was 1.39-fold that of the lowest risk therapy, oxcarbazepine (6.3%). Lithium was non-statistically significantly different from quetiapine. While lithium conferred a higher risk when compared to all other treatments combined as a group, hypothyroidism risk error bars overlapped for all drugs. Treatment (p = 3.86e-3), age (p = 6.91e-10), sex (p = 3.93e-7), and thyroid testing (p = 2.79e-87) affected risk. Patients taking lithium were tested for hypothyroidism 2.26-3.05 times more frequently than those on other treatments.

Thyroid abnormalities occur frequently in patients with BD regardless of treatment. Therefore, patients should be regularly tested for clinical or subclinical thyroid abnormalities on all therapies and treated as indicated to prevent adverse effects of hormone imbalances on mood.

Lithium, which is frequently used in the treatment of mood disorder, can lead to various types of thyroid dysfunctions. Although clinical examination and biochemical assessment are fundamental to any thyroid work-up of lithium-treated patients, assessment findings vary widely depending on the investigator. Ultrasonographic measurement of thyroid volume has, therefore, been performed in lithium treatment populations and found to be a sensitive tool.

We aimed to determine and compare thyroid gland volume using Ultrasonography and laboratory parameters, (thyroid-stimulating hormone [TSH], T3, and T4) in long-term lithium and other mood stabilizers treated patients with mood disorder.

In this cross-sectional study, we performed ultrasonography examinations and thyroid function test of 30 patients on lithium treatment and 30 patients on other mood stabilizers.

The ultrasonographically measured thyroid volume was significantly increased in patients receiving lithium therapy as compared to the patients receiving other mood stabilizers. The total triiodothyronine (T3) was significantly increased with trends toward increased total thyroxine (T4) and decreased TSH in patients receiving lithium therapy as compared to the patients receiving other mood stabilizers.

These results highlight the need of including ultrasonographic measurement of thyroid volume as a part of standard thyroid work-up before initiating lithium prophylaxis and during follow-up. Additional studies on the incidence and mechanism of lithium associated hyperthyroidism are needed.

Lithium was known to cause thyroid dysfunction and most commonly subclinical hypothyroidism (SCH). The aim of this study is to determine the prevalence of Lithium associated thyroid dysfunction and to identify risk factors associated with development of SCH in patients receiving Lithium.

A retrospective cross-sectional study was conducted. Subjects who developed elated thyroid stimulating hormone (TSH) were compared with those who remained euthyroid with Lithium treatment. Logistic regression and survival analysis were applied to identify the significant factors associated with SCH.

The prevalence of Lithium associated with SCH was 31.7 %. The significant risk factors associated with increased risk of SCH included being female, higher serum Lithium level, concomitant use of Valproate Sodium and use of antidepressant. Use of depot injection was associated with decreased risk of SCH.

Use of depot and avoidance of Valproate or antidepressant should be taken into account before starting patient on Lithium treatment. Thyroxine replacement should be considered when Lithium associated SCH was identified.

Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management.

Polyuria increases the risk of dehydration and lithium toxicity in lithium-treated patients. Risk factors have been inconsistently described and the variance of this adverse effect remains poorly understood. This study aimed to establish independent risk factors for polyuria in a community, secondary-level lithium-treated sample of patients.

This was a cross-sectional study of the lithium-treated patients attending a general adult and an old age psychiatry service. Participants completed a 24-hour urine collection. Urine volume and the presence of polyuria were the outcomes of interest. The relationship between outcome and the participant's demographic and clinical characteristics was explored with univariable and multivariable analysis.

A total of 122 participants were included in the analysis, with 38% being diagnosed with polyuria. Female gender and increased body weight independently predicted the presence of polyuria (standardized regression coefficient 1.01 and 0.94, respectively; p = 0.002 and p = 0.003, respectively). Female gender and increased body weight, lithium dose, and duration of lithium treatment independently predicted higher 24-hour urine volumes (standardized regression coefficients 0.693, p < 0.0005; 0.791, p < 0.0005; 0.276, p = 0.043; 0.181, p = 0.034, respectively). Of three different weight metrics, lean body weight was the most predictive.

Female gender and increased body weight explain part of the variance of this adverse effect. Both risk factors offer fresh insights into the pathophysiology of this potentially reversible and dangerous adverse effect of lithium treatment. Future research should focus on understanding the differences between the genders and between different body compositions in terms of lithium pharmacokinetics and pharmacodynamics.

The purpose of this study was to determine if the known side effects of lithium in adults may be generalized to younger patients with psychiatric disorders.

A retrospective naturalistic study design was used. Data were collected from the database of a tertiary pediatric medical center covering the years 1994-2010. Included were patients hospitalized for bipolar and non-bipolar disorders and treated with lithium, alone or in combination with other medications. The electronic medical files were reviewed for changes in thyroid and kidney function and for hematological parameters during the course of treatment.

Sixty-one patients 12.5-20.4 years of age (mean 16.94±1.66) met the study criteria: 33 with bipolar disorder and 28 with a non-bipolar disorder. Mean duration of lithium treatment (mean lithium blood level, 0.73±0.24 mEq/L) was 193.68±254.35 days. Mean levels of thyroid-stimulating hormones (TSH) rose significantly from baseline to last measurement (3.16±2.68 vs. 1.52±0.92 mU/L; paired t=-5.19, df=50, p<0.001); in 25% of patients, TSH levels at the last measurement were above normal (≥4 mU/L). Only one patient developed TSH values >10 mU/L (the threshold considered clinically significant). Positive correlation was found between pre- and posttreatment TSH levels (Pearson's r=0.60; n=51, p<0.05). White blood cell count (WBC) also increased significantly following lithium treatment (7195±2151 vs. 7944±2096 cells/mm(3); t=2.83, df=60, p=0.006). No significant changes were noted in serum creatinine levels. There was no difference in these parameters between patients treated with lithium alone or in combination with other medications.

Lithium treatment in adolescents with bipolar or non-bipolar disorders is associated with a significant increase in blood TSH levels and WBC count. Lithium-treated adolescent inpatients with a high basal TSH level may be at risk of developing pituitary-thyroid axis dysregulation. Therefore, baseline measurement of thyroid functions and serial monitoring throughout treatment are recommended.

Laboratory tests are essential for accurate diagnosis and cost-effective management of thyroid disorders. When the clinical suspicion is strong, hormonal levels just confirms the diagnosis. However, in most patients, symptoms are subtle and unspecific, so that only biochemical tests can detect the disorder. The objective of this article is to do a critical analysis of the appropriate use of the most important thyroid function tests, including serum concentrations of thyrotropin (TSH), thyroid hormones and antithyroid antibodies. Through a survey in the MedLine database, we discuss the major pitfalls and interferences related to daily use of these tests and recommendations are presented to optimize the use of these diagnostic tools in clinical practice.

The study was designed to test an audit-based quality improvement programme (QIP) addressing lithium prescribing and monitoring in UK mental health services.

A baseline clinical audit was conducted against the following standards: (i) measurement of renal and thyroid function before initiating treatment with lithium and (ii) recommended monitoring of serum lithium and renal and thyroid function during maintenance treatment. A re-audit was conducted at 18 months and a supplementary audit at three years.

Data were submitted for patients at baseline (n = 3,373), re-audit (n = 3,647), and supplementary audit (n = 5,683), 57% of whom had bipolar disorder. The baseline findings prompted a patient safety alert issued by the National Patient Safety Agency. By supplementary audit, the proportion of patients having four serum lithium tests over the previous year had increased from 30% at baseline to 48%, and the respective proportions that had two tests of renal function from 55% to 70% and thyroid function from 49% to 66%. Elderly patients and those prescribed a drug known to interact with lithium were not more likely to be monitored in line with the audit standards. Between baseline and supplementary audit, the proportion of patients with a diagnosis of bipolar disorder prescribed an antidepressant increased from 36% to 41%.

Improvements in biochemical monitoring of lithium treatment were achieved over time with participation in a QIP that included benchmarking of performance against clinical standards and customized change interventions. Nevertheless, gaps remain between the standard and current practice. Antidepressants are frequently prescribed in patients with bipolar disorder despite a paucity of evidence supporting their efficacy.

These guidelines are based on a first edition that was published in 2004, and have been edited and updated with the available scientific evidence up to October 2012. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the long-term treatment of bipolar disorder in adults.

Material used for these guidelines are based on a systematic literature search using various data bases. Their scientific rigor was categorised into six levels of evidence (A-F) and different grades of recommendation to ensure practicability were assigned.

Maintenance trial designs are complex and changed fundamentally over time; thus, it is not possible to give an overall recommendation for long-term treatment. Different scenarios have to be examined separately: Prevention of mania, depression, or an episode of any polarity, both in acute responders and in patients treated de novo. Treatment might differ in Bipolar II patients or Rapid cyclers, as well as in special subpopulations. We identified several medications preventive against new manic episodes, whereas the current state of research into the prevention of new depressive episodes is less satisfactory. Lithium continues to be the substance with the broadest base of evidence across treatment scenarios.

Although major advances have been made since the first edition of this guideline in 2004, there are still areas of uncertainty, especially the prevention of depressive episodes and optimal long-term treatment of Bipolar II patients.

Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. Thyroid abnormalities associated with treatment with lithium have been widely reported in medical literature to date. These include goitre, hypothyroidism, hyperthyroidism and autoimmune thyroiditis. This current review explores the varied thyroid abnormalities frequently encountered among patients on lithium therapy and their management, since lithium is still a fundamental and widely drug used in psychiatry and Internal Medicine.

PubMed database and Google scholar were used to search for relevant English language articles relating to lithium therapy and thyroid abnormalities up to December 2012. The search terms used were lithium treatment, thyroid abnormalities, thyroid dysfunction, goitre, hypothyroidism, hyperthyroidism, thyrotoxicosis, autoimmune thyroiditis, lithium toxicity, treatment of affective disorders and depression and side effects of antipsychotic drugs. Reference lists of the identified articles were further used to identify other studies.

Lithium affects normal thyroid functioning through multiple mechanisms. At the cellular level, it decreases thyroid hormone synthesis and release. It also decreases peripheral deiodination of tetraiodothyronine (T4) or thyroxine by decreasing the activity of type I 5' de-iodinase enzyme. Hypothyroidism and goitre (clinically and/ultrasonographically detected) are the most prevalent thyroid abnormalities among patients on long term lithium therapy. Lithium induced hyperthyroidism is very infrequent. Lithium increases the propensity to thyroid autoimmunity in susceptible individuals due to its effect of augmenting the activity of B lymphocytes and reducing the ratio of circulating suppressor to cytotoxic T cells.

Thyroid function tests (serum thyroid stimulating hormone, free thyroid hormones-T4 and triiodothyronine [T3] concentrations and thyroid auto-antibodies) and assessment of thyroid size clinically and by thyroid ultrasonography ought to be performed among patients initiating lithium therapy at baseline and later annually. More frequent assessment of thyroid function status and size during the course of therapy is recommended among middle aged females (≥50 years), patients with a family history of thyroid disease and those positive for thyroid auto-antibodies (anti-thyroid peroxidase and TSH receptor antibodies).

Detection of antithyroid peroxidase antibody (TPOAb) is widely used in the diagnosis of autoimmune thyroiditis (AIT), but no research has evaluated the diagnostic accuracy of TPOAb detection using histopathologic reference standards. To fill this research gap, this study assessed the diagnostic accuracy of detection of TPOAb and that of other serological markers in asymptomatic patients who had been diagnosed with AIT by histopathologic analysis after thyroid surgery. After review of patient records, 598 patients who had undergone thyroid nodule surgery were enrolled for examination for thyroid parenchyma by a pathologist and classification into no co-existing lymphocytic thyroiditis, Hashimoto thyroiditis, or non-Hashimoto type of lymphocytic thyroiditis (NHLT). The correlation between patient serological data and thyroid parenchyma pathology was analyzed. Statistically significant differences (P < 0.05) were found between co-existing lymphocytic thyroiditis and no co-existing lymphocytic thyroiditis groups regarding thyroid-stimulating hormone (TSH) and TPOAb levels. And, TPOAb titer was significantly associated with the degree of inflammation. An abnormal TPOAb titer was found in 86 of the 598 patients (14.4 %) and the specificity of TPOAb detection for AIT diagnosis was found to be 96.9 %. The prevalence of Hashimoto thyroiditis and NHLT in the 560 papillary thyroid cancer (PTC) patients was found to be 7.9 and 17.9 %, respectively. The results indicate that TPOAb titer is associated with the degree of thyroid inflammation and that detection of TPOAb is a very specific means of diagnosing AIT. The results also indicate that the incidence of AIT and PTC coexistence is relatively high.

Despite more that 60 years of clinical experience, the effective use of lithium for the treatment of mood disorder, in particular bipolarity, is in danger of becoming obsolete. In part, this is because of exaggerated fears surrounding lithium toxicity, acute and long-term tolerability and the encumbrance of life-long plasma monitoring. Recent research has once again positioned lithium centre stage and amplified the importance of understanding its science and how this translates to clinical practice.

The aim of this paper is to provide a sound knowledge base as regards the science and practice of lithium therapy.

A comprehensive literature search using electronic databases was conducted along with a detailed review of articles known to the authors pertaining to the use of lithium. Studies were limited to English publications and those dealing with the management of psychiatric disorders in humans. The literature was synthesized and organized according to relevance to clinical practice and understanding.

Lithium has simple pharmacokinetics that require regular dosing and monitoring. Its mechanisms of action are complex and its effects are multi-faceted, extending beyond mood stability to neuroprotective and anti-suicidal properties. Its use in bipolar disorder is under-appreciated, particularly as it has the best evidence for prophylaxis, qualifying it perhaps as the only true mood stabilizer currently available. In practice, its risks and tolerability are exaggerated and can be readily minimized with knowledge of its clinical profile and judicious application.

Lithium is a safe and effective agent that should, whenever indicated, be used first-line for the treatment of bipolar disorder. A better understanding of its science alongside strategic management of its plasma levels will ensure both wider utility and improved outcomes.

Accumulating evidence suggests that hypothalamo-pituitary-thyroid (HPT) axis dysfunction is relevant to the pathophysiology and clinical course of bipolar affective disorder. Hypothyroidism, either overt or more commonly subclinical, appears to the commonest abnormality found in bipolar disorder. The prevalence of thyroid dysfunction is also likely to be greater among patients with rapid cycling and other refractory forms of the disorder. Lithium-treatment has potent antithyroid effects and can induce hypothyroidism or exacerbate a preexisting hypothyroid state. Even minor perturbations of the HPT axis may affect the outcome of bipolar disorder, necessitating careful monitoring of thyroid functions of patients on treatment. Supplementation with high dose thyroxine can be considered in some patients with treatment-refractory bipolar disorder. Neurotransmitter, neuroimaging, and genetic studies have begun to provide clues, which could lead to an improved understanding of the thyroid-bipolar disorder connection, and more optimal ways of managing this potentially disabling condition.

Lithium has long been recognised for its mood-stabilizing effects in the management of bipolar disorder (BD) but in practice its use has been limited because of real and 'imagined' concerns. This article addresses the need for lithium to be measured with respect to its clinical and functional effects. It introduces a visual scale, termed lithiumeter, which captures the optimal lithium plasma levels for the treatment of BD.

  Key words pertaining to lithium's administration, dosing, and side effects as well as its efficacy in acute and long-term treatment of BD were used to conduct an electronic search of the literature. Relevant articles were identified by the authors and reviewed.

This paper outlines the considerations necessary prior to initiating lithium therapy and provides a guide to monitoring lithium plasma levels. Current recommendations for optimal plasma lithium levels in the management of BD are then discussed with respect to indications for use in the acute phases of the illness and maintenance therapy. The risks associated with lithium treatment are also discussed.

The lithiumeter provides a practical guide of optimal lithium levels for the clinical management of BD.

Sex is clearly important in unipolar mood disorder with compelling evidence that depression is approximately twice as common in women than in men. In the case of bipolar disorder, however, it is widely perceived that the reported equal rate of illness in men and women reflects no important gender distinctions. In this paper we review the literature on gender differences in bipolar illness and attempt to summarize what is known and what requires further study. Despite the uncertainties that remain some conclusions can be drawn. Most studies, but not all, report an almost equal gender ratio in the prevalence of bipolar disorder but the majority of studies do report an increased risk in women of bipolar II/hypomania, rapid cycling and mixed episodes. Important gender distinctions are also found in patterns of co-morbidity. No consistent gender differences have been found in a number of variables including rates of depressive episodes, age and polarity of onset, symptoms, severity of the illness, response to treatment and suicidal behaviour. Unsurprisingly, however, perhaps the major distinction between men and women with bipolar disorder is the impact that reproductive life events, particularly childbirth, have on women with this diagnosis.

There is a significant dilemma when underlying medical disorders present as psychiatric conditions. It is important to identify the medical condition because treatment and management strategies need to be directed to the presenting symptoms and also to the underlying medical condition for successful treatment of the patient. Some systemic disorders present with psychiatric manifestations more often than others. The pattern of psychiatric disturbance seen may be specific for a particular medical disorder but may also be varied. Many drug formulations and medications also may produce psychiatric presentations. This article considers the management of nonpsychiatric medical conditions presenting with psychiatric manifestations.

The use of lithium for the treatment of mania, prophylaxis of bipolar disorder and augmentation of antidepressants in treatment-refractory unipolar depression is supported by British Association for Psychopharmacology and National Institute for Health and Clinical Excellence guidelines. We describe prescribing patterns with lithium in a large sample of patients with affective disorders. Data were collected during a baseline clinical audit of the quality of lithium monitoring, conducted by the Prescribing Observatory for Mental Health. Thirty-five National Health Service Trusts submitted data for 2776 patients with a diagnosis of affective illness (ICD10 F30-39), 1919 (69%) of whom had bipolar affective disorder. The last recorded lithium level was below the therapeutic range (<0.4 mmol/L) in one in 10 patients. Co-prescribing was common; 57% of bipolar patients were prescribed an antipsychotic and 77% of those with other affective disorders, an antidepressant. We conclude that serum lithium levels within the therapeutic range are maintained in the majority of patients. A high proportion of patients are co-prescribed other psychotropic drugs; such prescribing is consistent with evidence-based treatment guidelines and may reflect difficulty managing the symptoms of affective disorders with lithium monotherapy. A significant minority of patients prescribed lithium had a sub-therapeutic blood level and so may be at high risk of relapse.

Thyroid peroxidase-specific autoantibodies (TPO Abs) are mostly measured in patients with autoimmune thyroid diseases. The aim of this study was to compare TPO Ab concentrations measured by two radioimmunoassays.

Our investigation included 38 patients. Sera concentrations of TPO Abs were measured by using Cis biointernational (France) and Immunotech (Czech Republic) assays.

Concentrations obtained by two assays were extensively different. The values measured by Cis biointernational assay were higher than ones obtained by Immunotech assay. The statistical arrangement of results showed the direct correlation between the two assays, with the coefficient of agreement R = 0.6239 (p < 0.001). The analysis of relative values (ratio of measured and upper limit values given by the manufacturer) demonstrated the statistically significant difference (p = 0.003) between values measured by Cis biointernational (18.94 +/- 37.22) and by Immunotech assay (4.22 +/- 8.22) concerning the distinction between normal and raised concentrations of TPO Abs. The agreement of results (enhanced or normal TPO Ab concentrations in both tests) was shown in 30 sera samples (78.95%), but in residual 8 sera (21.05%) normal TPO Ab concentrations were obtained by Immunotech, and enchanced by Cis biointernational assay. There is no difference in capability of distinction between normal and pathological results between the two tests (chi12 = 3.484, p > 0.05). The highest concentration of TPO Ab measured by Cis biointernational assay was not the highest one in Immunotech assay, which might be a reflection of different specificity of antibodies used in two diagnostic tests.

TPO Ab concentrations obtained by Cis biointernational and Immunotech assays are very different. In several sera samples, normal concentrations of TPO autoantibodies were obtained by Immunotech assay and enhanced by Cis biointernational assay. The highest value obtained by one is not the highest value measured by another assay we used.

One in 200 people receive lithium for treatment of bipolar disorder. The common clinical side effects of the drug are goitre in up to 40% and hypothyroidism in about 20%. Lithium increases thyroid autoimmunity if present before therapy. Treatment with levothyroxine is effective and lithium therapy should not be stopped. Lithium may cause hyperthyroidism due to thyroiditis or rarely Graves' disease. As lithium inhibits thyroid hormone release from the thyroid gland it can be used as an adjunct therapy in the management of severe hyperthyroidism. It also increases thyroidal radioiodine retention and may be effective in reducing administered activity in hyperthyroidism. There is no clinical benefit of lithium therapy in thyroid cancer. More research is required on the cellular proliferative effects of lithium as well as its impact on the immune system.

Safety monitoring is an important aspect of bipolar disorder treatment, as mood-stabilising medications have potentially serious side effects, some of which may also aggravate existing medical comorbidities. This paper sets out the International Society for Bipolar Disorders (ISBD) guidelines for the safety monitoring of widely used agents in the treatment of bipolar disorder. These guidelines aim to provide recommendations that take into consideration the balance between safety and cost-effectiveness, to highlight iatrogenic and preventive clinical issues, and to facilitate the broad implementation of therapeutic safety monitoring as a standard component of treatment for bipolar disorder.

These guidelines were developed by an ISBD workgroup, headed by the senior author (MB), through an iterative process of serial consensus-based revisions. After this, feedback from a multidisciplinary group of health professionals on the applicability of these guidelines was sought to develop the final recommendations.

General safety monitoring recommendations for all bipolar disorder patients receiving treatment and specific monitoring recommendations for individual agents are outlined.

These guidelines are derived from evolving and often indirect data, with minimal empirical cost-effectiveness data available to provide guidance. These guidelines will therefore need to be modified to adapt to different clinical settings and health resources. Clinical acumen and vigilance remain critical ingredients for safe treatment practice.

Lithium use in mental diseases has changed over the years but remains a cornerstone of treatment in bipolar disorders. In two companion papers, we have reviewed existing (and especially recent) data on lithium efficacy and updated basic knowledge regarding the practical fundamentals of lithium therapy. The present paper reviews safety data on lithium available to date. Gastrointestinal pain or discomfort, diarrhoea, tremor, polyuria, nocturnal urination, weight gain, oedema, flattening of affect and exacerbation of psoriasis are typical complaints of patients receiving long-term lithium therapy. Renal involvement results in a reduced urinary concentrating capacity, expressed as obligate polyuria, with secondary thirst. With long-term therapy, this may result in nephrogenic diabetes insipidus. In addition, glomerular filtration rate falls slightly in about 20% of patients. The view that only a few patients receiving long-term lithium are at increased risk of glomerular impairment and progressive renal insufficiency should be regarded with caution. The risk is increased in case of concomitant diseases or medications. Lithium treatment may inhibit thyroid hormone release and induce goitre. Consequently, the prevalence of both overt and subclinical hypothyroidism is increased, with circulating thyroid auto-antibodies frequently being found. Much less commonly, thyrotoxicosis may also develop in association with lithium therapy. Long-term lithium treatment may also be associated with persistent hyperparathyroidism and hypercalcaemia, as well as with hypermagnesaemia. Overweight of up to 4-10 kg is found in approximately 30% of lithium-treated patients. Most neurological manifestations are benign, for example, the fine postural and/or action tremor present in 4-20% of patients. This is increased by high caffeine consumption and concomitant use of other psychotropic agents. A number of rare, potentially serious neurological adverse effects have been reported, including extrapyramidal symptoms, 'pseudotumour cerebri' or occasionally cerebellar symptoms. Severe neurological sequelae are exceptional. Cognitive disturbances are often mentioned as a lithium-related adverse effect. The few controlled studies do show a statistically significant negative effect of lithium on memory, vigilance, reaction time and tracking. There are frequent reports of mild effects of lithium on cognition at therapeutic serum concentrations. A number of deaths associated with lithium treatment have been reported. The most serious issue is that of non-accidental overdose, i.e. either long-term overdosage or acute overdose on long-term treatment. Progressive renal insufficiency, an exceptional complication of long-term lithium therapy, may also have a fatal outcome. In relation to pregnancy, lithium salts are rated as category D (positive evidence of risk). Therefore, prescription of lithium should be avoided during the first trimester of pregnancy unless the benefit to the mother exceeds the risk to the fetus. Although lithium transfer into breast milk is well established, the long-term fate of babies breast-fed by mothers receiving lithium therapy is unknown. Whether lithium therapy is safe in breast-feeding women is controversial. Although there is no absolute contraindication, it is known that the kidney is particularly sensitive to lithium just after birth. Intoxication in patients on long-term treatment with lithium in the absence of history of acute ingestion is not rare. Contributing factors include change in daily dose, long-term high dosage, kidney disease or drug interaction. In suspected cases, serum concentrations should be obtained early and repeatedly. In addition to supportive measures, haemodialysis is the treatment of choice for severe cases. Thorough knowledge of the limitations and drawbacks of lithium therapy is mandatory for its optimal use, especially at a time when its risk/benefit profile needs to be compared accurately with that of antiepileptic drugs and other mood stabilizing medications.