ECG changes associated with lithium intoxication : a study based on the lisie project

INTRODUCTION: It currently remains unclear in how far supratherapeutic lithium serum concentrations can affect the cardiac conduction system. Prolonged QT interval, arrhythmias and cardiac death have all been anecdotally reported, but the systematic studies are few. OBJECTIVES: To examine ECG changes occurring with supratherapeutic lithium concentrations that have given rise to lithium toxicity. METHODS: We examined all episodes of lithium intoxication defined as serum lithium level (≥ 1.5 mmol/L). We analyzed ECG before, during and after intoxication and recorded ECG changes. These, we then assessed according to type of intoxications, clinical and other pharmacological characteristics. The study is based on 20-year data (1997-2020) from the retrospective cohort study (LiSIE) in the Swedish region of Norrbotten. RESULTS: Of 1101 patients treated with lithium, 77 patients had experienced lithium intoxications. 12 patients had more than one episode of intoxication, yielding 91 episodes. 39 had ECG available both as reference and during lithium intoxication. We found no statistically significant prolongation of the QTc interval during lithium intoxication, compared to respective reference ECG (p = 0.364). Heart rate during lithium intoxication was significantly lower, mean 73 beats/min (SD 16,8, range 43 - 112), compared to the reference ECG, mean 79 beats/min (SD 15,3, range 48-112; p = 0.006). No patient died. All findings were independent of whether an intoxication was acute or chronic. CONCLUSIONS: In our study, heart rate was significantly lower during episodes of intoxication. However, this decrease was of no clinical relevance in most cases. Lithium intoxication was not associated with prolonged QT time. DISCLOSURE: M. Ott: scientific advisory board member of Astra Zeneca, Sweden. U. Werneke: received funding for educational activities on behalf of Norrbotten Region; Astra Zeneca, Eli Lilly, Janssen, Novartis, Otsuka/Lundbeck, Servier, Shire, Sunovion. Others: Non

Monoaminoxidase inhibitors as a cause of serotonin syndrome : a systematic case review based on meta-analytic principles

INTRODUCTION: Serotonin syndrome (SS) is a toxic state characterized by increased serotonin activity. It has been suggested that severe serotonin syndrome usually involves monoaminoxidase inhibitors (MAOIs). OBJECTIVES: To quantify in how far severe SS is associated with MAOIs. METHODS: Systematic review and quantitative analysis of all SS cases published between 1 January 2004 and 31 December 2014. Severe SS was defined as cases, either requiring intensive care or resulting in death. Cases were included if they met the diagnostic criteria for SS according to at least one of the three diagnostic criteria systems (Hunter, Radomski and Sternbach). RESULTS: Of the 299 included cases, 118 (39%) met the definition for severe SS. Eight cases had insufficient information to enable severity classification. Of the severe cases, 48 (40%) involved a MAOI. Of these, 67% related to psychiatric MAOIs, such as phenelzine and moclobemide and 33% to a somatic MAOI, such as methylene blue and linezolid. Of the remaining 173 non-severe SS cases, 24 cases (13%) involved a MAOI. In these, 12% related to a psychiatric MAOI and 83% to a somatic MAOI. One case (4%) had a combination of both. The odds ratio for MAOI involvement in severe versus non-severe serotonin syndrome was 4.3 (CI 2.4 – 7.5; p < 0.001). CONCLUSIONS: In the majority of published case reports, drugs other than MAOIs are involved in serotonin syndrome, even in severe cases. MAOIs are, however, more common in severe serotonin syndrome than in non-severe cases. CONFLICT OF INTEREST: M. Ott: scientific advisory board member of Astra Zeneca, Sweden. U. Werneke: received funding for educational activities on behalf of Norrbotten Region; Astra Zeneca, Eli Lilly, Janssen, Novartis, Otsuka/Lundbeck, Servier, Shire, Sunovion. Others: Non

Effects of toxic lithium levels on ECG : findings from the LiSIE retrospective cohort study

(1) Background: Few studies have explored the impact of lithium intoxication on the heart. (2) Methods: We examined electrocardiogram (ECG) changes associated with lithium intoxication in the framework of the LiSIE (Lithium-Study into Effects and Side Effects) retrospective cohort study. We analysed ECGs before, during, and after intoxication. (3) Results: Of the 1136 patients included, 92 patients had experienced 112 episodes of lithium intoxication. For 55 episodes, there was an ECG available at the time; for 48 episodes, there was a reference ECG available before and/or after the lithium intoxication. Lithium intoxication led to a statistically significant decrease in heart rate from a mean 76 beats/min (SD 16.6) before intoxication to 73 beats/min (SD 17.1) during intoxication (p = 0.046). QTc correlated only weakly with lithium concentration (ρ = 0.329, p = 0.014). However, in 24% of lithium intoxication episodes, there were QT prolongations. In 54% of these, QTc exceeded 500 ms; patients with chronic intoxications being more affected. (4) Conclusions: Based on summary statistics, effects of lithium intoxication on HR and QTc seem mostly discrete and not clinically relevant. However, QT prolongation can carry a risk of becoming severe. Therefore, an ECG should always be taken in patients presenting with lithium intoxication

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder : a 17-year follow-up on the LiSIE retrospective cohort study

Introduction: Mood stabilisers and other psychotropic drugs can lead to serious adverse drug events (ADEs). However, the incidence remains unknown. We aimed to (a) determine the incidence of serious ADEs in patients with bipolar or schizoaffective disorders, (b) explore the role of lithium exposure, and (c) describe the aetiology. Methods: This study is part of the LiSIE (Lithium—Study into Effects and Side Effects) retrospective cohort study. Between 2001 and 2017, patients in the Swedish region of Norrbotten, with a diagnosis of bipolar or schizoaffective disorder, were screened for serious ADEs to psychotropic drugs, having resulted in critical, post-anaesthesia, or intensive care. We determined the incidence rate of serious ADEs/1,000 person-years (PY). Results: In 1,521 patients, we identified 41 serious ADEs, yielding an incidence rate of 1.9 events per 1,000 PY. The incidence rate ratio (IRR) between ADEs with lithium present and causally implicated and ADEs without lithium exposure was significant at 2.59 (95% CI 1.20–5.51; p = 0.0094). The IRR of ADEs in patients &lt;65 and ≥65 years was significant at 3.36 (95% CI 1.63–6.63; p = 0.0007). The most common ADEs were chronic lithium intoxication, oversedation, and cardiac/blood pressure-related events. Discussion: Serious ADEs related to treatment of bipolar (BD) or schizoaffective disorder (SZD) were uncommon but not rare. Older individuals were particularly at risk. The risk was higher in individuals exposed to lithium. Serum lithium concentration should always be checked when patients present with new or unclear somatic symptoms. However, severe ADEs also occurred with other mood stabilisers and other psychotropic drugs