Some pharmacological aspects relating to the issue of possible neurotoxic interactions during combined lithium-neuroleptic therapy
✍ Scribed by John L. Waddington
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 398 KB
- Volume
- 5
- Category
- Article
- ISSN
- 0885-6222
No coin nor oath required. For personal study only.
✦ Synopsis
The debate on the issue of whether serious neurotoxic reactions are more likely or more problematic during combined lithium-neuroleptic therapy, in comparison with either agent given alone, has not yet been satisfactorily resolved. Clinical pharmacokinetic studies d o not indicate any profound effects of either drug on the plasma levels, distribution, and clearance of the other when given concurrently. At the preclinical pharmacodynamic level, a variety of fundamental cellular processes have been studied both in vitro and in vivo, but these either fail to indicate any basis for toxic synergism or else demonstrate interactions only at very high concentrations of questionable clinical relevance. In animal behavioural studies, there is no convincing evidence that such neurotoxic reactions occur during combined lithium-neuroleptic administration. However these pharmacological studies must be interpreted conservatively. As such approaches also fail to model or explain the phenomena of tardive dyskinesia and neuroleptic malignant syndrome, negative findings cannot be regarded as conclusive.