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in addition to the tcas, lithium and clozapine, serum levels indicative of an increased risk of toxicity have also been documented for those anticonvulsants with mood stabilizing properties (i.e. the obverse problem is that of unacceptably low concentrations, which may be a relevant factor in either failure to respond or relapse. tdm should clarify whether the problem is due to subtherapeutic drug concentrations or to inefficacy of the drug in a particular patient. while the use of slow-release (sustained, controlled-release) preparations has been proposed as a means of diminishing postdose variation in serum concentrations and associated adverse effects, this has yet to be established empirically [19]. the american psychiatric association practice guidelines for the treatment of patients with bipolar disorder [23] recommend that levels be titrated to serum concentrations of 0.5–1.2 mmol l−1 for the acute treatment of mania. [35] found no difference in the outcome of bipolar patients ran-domly allocated to either continue lithium at a level of 0.8–1.2 mmol l−1 or to decrease to 0.45–0.79 mmol l−1.

the only investigation of the relationship between serum valproate concentration and response in mania has been that of bowden et al. no therapeutic concentration ranges have been demonstrated for any of the ssris [52] and toxicity is in general not relevant as thesse drugs have a wide therapeutic index. while this technique has a dynamic range consistent with therapeutic concentrations of the tcas, a limitation is the considerable cross-reactivity of tertiary and secondary amine tcas, as well as with structurally similar drugs such as the antipsychotic chlorpromazine. in the elderly, tca levels may be increased by reduced hepatic metabolism and blood flow, and changes in the volume of distribution. [73] found a benefit to cost ratio of 2.5 for the prospective dosing technique of browne et al. the therapeutic value of rra has yet to be proven. since these drugs are used long-term there may be a case for phenotyping or genotyping patients at the start of such therapy.

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