Lithium adverse effects

A study in 14 treatment-resistant depressed patients aged between 61 and 82 found that 7 showed eomplete improvement and 3 showed partial improvement, 3 to 21 days after lithium was added to treatment with the tricyclic or related antidepressants. Lithium adverse effects occurred in 6 patients 4 of whom stopped lithium as a result. One of them was successfully restarted at a lower dose. Tremor was the most frequent adverse effect, and reversible neurotoxicity with a stroke-like syndrome was the most severe. The antidepressants used were amitriptyline, doxepin, maprotiline and trazodone. A meta-analysis of 9 studies on the acute treatment of unipolar or bipolar depression indicated that the combined use of a mood stabiliser (lithium in 6 studies) and a tricyclic antidepressant was associated with an increased risk of switches into (hypo)mania, when compared with a mood stabiliser alone. It was suggested that monotherapy with a mood stabiliser should be tried to see if it is effective, before adding an antidepressant. Tricyclics were considered to be second-line antidepressants, with SSRIs the preferred choice. ... 

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Electroconvulsive therapy (ECT) is used for severe mania or depression during pregnancy and for mixed episodes prior to treatment, anticonvulsants, lithium, and benzodiazepines should be tapered off to maximize therapy and minimize adverse effects. 

Lithium and other mood-stabilizing drugs require baseline and routine laboratory monitoring to help determine medical appropriateness for initiation of therapy and monitoring of potential adverse effects. Guidelines for such monitoring are outlined in Table 36-6. 

A 36-year-old male with a bipolar disorder is treated with lithium. Among the following adverse effects, which is associated with lithium treatment ... 

Use standard therapeutic serum concentration ranges if clinically indicated if partial response or breakthrough episode, adjust dose to achieve higher serum concentrations without causing intolerable adverse effects valproate is preferred over lithium for mixed episodes and rapid cycling lithium and/or lamotrigine is preferred over valproate for bipolar depression. 

On the other hand, since most of these reactions are thermally activated, their kinetics are accelerated by the rise in temperature in an Arrhenius-like manner. Therefore, within a much shorter time scale, the adverse effect of these reactions could become rather significant during the storage or operation of the cells at elevated temperatures. In this sense, the long-term and the thermal stability of electrolytes can actually be considered as two independent issues that are closely intertwined. The study of temperature effects on electrolyte stability is made necessary by the concerns over the aging of electrolytes in lithium-based devices, which in practical applications are expected to tolerate certain high-temperature environments. The ability of an electrolyte to remain operative at elevated temperatures is especially important for applications that are military/space-related or traction-related (e.g., electric or hybrid electric vehicles). On the other hand, elevated tem-... 

This corrosion of the SEI by linear carbonate solvents would undoubtedly produce adverse effects on the performance of lithium ion cells. During longterm cycling, the damaged SEI has to be repaired constantly by the same electrochemical reactions that occurred in the initial formation process, which consumes the limited lithium ion source in the cell and increases the impedance at the electrode/ electrolyte interface. 

Lithium salts, generally in the form of the carbonate or bicarbonate, are rapidly absorbed from the gastrointestinal tract and reach a peak plasma concentration after 2- hours. Extreme fluctuations in blood lithium levels, which are associated with side effects such as nausea, diarrhoea and abdominal cramp, are reduced by using sustained release preparations. Lithium is not protein bound and therefore is widely distributed throughout the body water, which accounts for the adverse effects it has on most organ systems should it reach toxic levels. To avoid toxicity, and ensure optimal... 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Lithium ions. Lithium salts (e.g., acetate, carbonate) are effective in controlling the manic phase. The effect becomes evident approx. 10 d after the start of therapy. The small therapeutic index necessitates frequent monitoring of Li+ serum levels. Therapeutic levels should be kept between 0.8-1.0 mM in fasting morning blood samples. At higher values there is a risk of adverse effects. 

Most bore waters include high concentrations of at least one of the following chemical contaminants (Table 1) lithium (Li), boron (B as H3BO3), arsenic (As), hydrogen sulphide (H2S), mercury (Hg), and sometimes ammonia (NH3). If released into a river or lake, these contaminants can potentially damage aquatic life, terrestrial plants, and/or human health. The disposal of highly saline bore waters can also have an adverse effect on water quality. 

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. 

In partially responsive or nonresponsive patients, the first issue is to determine whether an individual is truly treatment-resistant, because many receive nontherapeutic doses and the potential for improvement may not be adequately tested. Thus, in some situations, more aggressive treatment (dose increase, augmentation) may be appropriate, if not precluded by adverse effects. In selected cases, it may also be helpful to monitor plasma levels to ensure that they are in a reasonable range (see Pharmacokinetics/Plasma Levels earlier in this chapter). If a patient continues to demonstrate significant symptoms after a sufficient trial (2 to 3 weeks), alternatives to switching to another antipsychotic may include the addition of lithium, an anticonvulsant, or a second antipsychotic agent. An antidepressant or anxiolytic may also be helpful, especially if affective or anxiety symptoms are prominent. 

Although initial reports concluded that low-dose lithium could augment the effect in patients partially responsive to an SSRI ( 373), subsequent reports have been less encouraging (374, 375). Furthermore, there is an increase in bothersome adverse effects when lithium is added to SSRI therapy (376). Both of these factors plus the need for TDM when using lithium has caused this approach to fall from favor in recent years. 

Like some other antidepressants and lithium, the MAOIs can also cause weight gain. Because they do not affect cholinergic receptors, they produce less constipation, dry mouth, and blurred vision, typically associated with the tricyclics. MAOIs do produce some similar adverse effects, particularly urinary hesitancy, possibly because... 

In summary, although lithium has revolutionized the treatment of bipolar disorder, its narrow therapeutic index, numerous adverse effects, and relative ineffectiveness in a large proportion of bipolar patients has led to an expanding number of alternative approaches, including the following ... 

Because lithium has a half-life of approximately 24 hours and it takes four to five half-lives to achieve steady-state at a fixed dose, blood levels should be obtained every 5 days until an adequate therapeutic concentration is achieved or adverse effects preclude further increases. Attempts to develop dose prediction formulae to obtain therapeutic concentrations more rapidly have been promising, but they have not enjoyed widespread utilization ( 101, 102 and 103). While premature monitoring may lead to higher than necessary dosing, more frequent measuring of levels may be warranted in patients with known sensitivity to lithium or if... 

Whenever possible, we prefer to treat with a mood stabilizer (e.g., lithium, VPA) alone, because of their specificity for bipolar disorder and to minimize adverse effects. This is particularly true in mild to moderately severe episodes of acute mania. In addition, if the patient can benefit from a single drug during the acute episode, this would support its benefit for maintenance and prophylactic purposes. Further, monotherapy diminishes the chance for potentially significant drug interactions and reduces cost. 

The major benefit of BZDs may be in diminishing some of the secondary symptoms of an acute exacerbation (e.g., insomnia, agitation, panic, and other general anxiety symptoms) that are not necessarily rapidly and specifically affected by lithium or antipsychotics. With this approach, exposure to antipsychotics may be precluded in some situations and kept to a minimum in others, thus avoiding the potential for more serious antipsychotic-induced adverse effects. Additionally, given the high comorbidity with alcohol abuse/dependence, concurrent withdrawal symptoms may also be managed with BZDs. 

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