Lithium, long-term potentiation

In this context, the first role of the laboratory is to detect specific adverse effects to target organs (see Role of the Laboratory later in this chapter). Monitoring will generally be tailored to the specific therapy used because of its known potential for causing certain problems. Examples include periodic blood counts with carbamazepine or clozapine and thyroid and renal function studies with long-term maintenance lithium. 

Lithium may facilitate the release of 5-HT, perhaps by increasing tryptophan uptake, enhancing 5-HT release through presynaptic autoreceptors, and/or by increasing activity at postsynaptic 5-HT receptors (i.e., act as a 5-HT agonist). Some data, however, question the long-term effect of lithium on 5-HT enhancement when studied in patients, as opposed to healthy control subjects ( 27). Similar to lithium, clonazepam can increase 5-HT synthesis and cerebrospinal fluid (CSF) levels of its major metabolite, 5-hydroxyindoleacetic acid. Other agents known to enhance 5-HT activity by different mechanisms have also shown initial promise as potential antimanic treatments (e.g., L-tryptophan, a 5-HT precursor). 

In summary, there is evidence for a higher relapse rate in patients not maintained on adequate levels of lithium, the potential for concurrent drugs (e.g., antidepressants) to exacerbate the disorder, a more rapid recurrence with abrupt discontinuation, and possible compromised future lithium responsiveness when it is stopped (43, 162).Compliance issues remain a major factor in providing adequate long-term treatment. 

Maintenance and prophylaxis with lithium, and perhaps other mood stabilizers, favorably alters the longitudinal course of a bipolar disorder. Thus, efforts to enhance long-term compliance are a necessary part of any overall strategy. The incidence of adverse or toxic events is relatively low, and close attention to the more clinically relevant consequences can usually prevent serious sequelae ( 198).An issue of critical importance for future research is the potential efficacy of alternative maintenance medication for those who fail to respond adequately to acute or long-term lithium therapy. 

Atypical antipsychotics such as aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are effective as monotherapy or adjunctive therapy with lithium and valproate in the treatment of acute mania. Some antipsychotics have the potential to cause adverse effects such as extrapyramidal reactions, sedation, depression, emotional blunting, sexual dysfunction, weight gain, and orthostatic hypotension. Prophylactic use of antipsychotics may be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed because of long-term adverse effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). ... 

This evidence suggests that lithium may exert some of its long-term benefits in the treatment of mood disorders via neuroprotective effects and that hthium may have potential therapeutic properties in neurodegenerative disorders. 

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