In the following section you will find different sorts of information on the biochemistry and physiological functions of lithium and on its use in clinical practice, including possible problems which can occur during lithium treatment.
Topics:
The Historical Background of Lithium Therapy and Prophylaxis
Biochemical and Physiological Effects of Lithium
Clinical Effects and Indications
Adverse Effects of Lithium Salts
The Pharmacoeconomics of Lithium Prophylaxis
Alternatives and Supplements to Lithium Treatment
Laboratory Methods for Monitoring Serum Lithium Levels
The Historical Background of Lithium Therapy and Prophylaxis (M. Schou)
Lithium was first used to treat depressive patients in the latter part of the 19th century, although the hypothesis upon which the therapy was based was actually incorrect. Therapeutic success was reported in a number of isolated cases.
The antimanic effect of lithium was discovered in 1949 and confirmed in a placebo-controlled, double-blind study in 1954.
 |
|
Schou and Baastrup met the Australian John Cade in the 50ies to discuss the first clinical experience with lithium salts.
|
During the 1960s lithium was found to prevent recurrences of both manic and depressive episodes. This prophylactic effect was first demonstrated in an open study using the mirror method, and subsequently (i.e. after 1970) confirmed in a number of double-blind, placebo-controlled discontinuation studies. Lithium prophylaxis was similarly efficacious in bipolar and unipolar patients.
An important historical event related to the safety and optimization of lithium prophylaxis occurred in the 1970s. Research emerged which indicated that long-term lithium use could possibly induce kidney damage. Through the exemplary joint efforts of many research teams, however, it was possible to rebut most of these alarming reports. Since the 1970s, researchers and physicians have recommended serum lithium levels slightly lower than those previously advocated.
An international multicenter study yielded strong evidence that mortality and suicide rates can be lowered by long-term lithium treatment – effects which have not been shown for any other long-term prophylactic treatment thus far.
back >>
Biochemical and Physiological Effects of Lithium
Cellular Transport and the Inorganic Biochemistry of Lithium (N.J. Birch)
The chemistry of lithium is unusual. Lithium atoms are very small, highly polarized, and have a high charge density. The chemical and biochemical properties of lithium are similar to those of magnesium, with which it shares a “diagonal relationship” in the periodic table. Because magnesium plays a crucial role in the regulation of biochemical systems, it has been theorized that lithium influences magnesium-dependent processes.
Lithium can be transported across membranes in five different ways. Of these, passive flux is important for the entry of lithium into cells, and sodium-lithium countertransport for the extrusion of lithium from cells. Lithium can presumably replace sodium in the sodium-sodium countertransport system, although the biological significance of the latter process is still unclear.
It appears that the concentration of lithium in cells does not reach the levels predicted by the Nernst equation. Rather, the intracellular lithium concentration is considerably lower than its concentration in blood or extracellular fluid. This is important for the models which have been proposed for its mechanism of action, as these must be able to explain the effects of lithium at intracellular concentrations of 0.1 mmol/l (i.e. similar to those seen in patients on lithium prophylaxis).
One hypothesis suggests that the biological effects of lithium are due to the role it plays at the cell periphery, where, for example, it may influence cell recognition, cell signaling mechanisms at the cell membrane, and certain immunological processes.
Position of lithium in the Periodic System
back >>
Lithium as a Trace Element (K. Lehmann)
In humans endogenous serum lithium levels normally range from 0.14-8.6 micromol/l, with a maximum level of 15.8 micromol/l.
These lithium serum levels are 3 orders of magnitude lower than those necessary for therapeutic/prophylactic treatment.
Scientists suspect that endogenous lithium in the human body has a physiological function, although sufficient evidence of this is still lacking.
Daily lithium intake in humans is dependent on both diet and the use of medications that contain lithium. With the latter, a total of 15 micromol to 0.66 mmol of lithium may be administered per day.
back >>
Effects of Lithium on Neurotransmitters and Second Messenger Systems (D. van Calker)
Studies examining the effect of lithium ions on the synthesis and metabolism of neurotransmitters have, thus far, yielded inconsistent results, failing to shed any light on the mechanism of action of lithium in vivo.
Lithium ions prevent the development of functional supersensitivity to dopamine and acetylcholine receptor stimulation, most likely by influencing second messenger systems.
Lithium ions increase basal cAMP levels and inhibit the neurotransmitter-stimulated accumulation of cAMP in the brain and other tissues.
Acute administration of lithium inhibits the stimulation of adenylyl cyclase, most likely through direct competition with magnesium, whose hydrated ionic radius is similar to that of lithium. The effects of chronic lithium treatment, however, probably result from (a) the modification of gene expression among components of the adenylyl cyclase system, especially G protein subunits (G_i, G_s), as well as from (b) a stabilization of the inactive trimeric form of the Gi protein. Lithium has been found to increase basal cAMP levels, which is most likely due to attenuation of the Gi protein and an increase – probably resulting from the effects of lithium on gene transcription – in the levels of adenylyl cyclase type I and type II mRNA.
At therapeutically relevant concentrations, lithium ions inhibit the hydrolysis of inositol mono-phosphatase to inositol. This leads to a depletion of inositol and a strong increase in diacylglycerol (DAG) in susceptible cells and tissues, depending on species and tissue type. Susceptibility is determined by the activity of a high-affinity inositol transport system, as well as by the degree to which the inositolphospholipid (IP) second messenger system is hormonally stimulated. Pronounced inositol depletion can lead to an inhibition of the IP system in affected cells, which is probably a result of attenuated IP synthesis and/or the activation of protein kinase C (PKC) through the accumulation of DAG.
Lithium exposure facilitates the activation of certain PKC isozymes, chronic activation of which can result in a downregulation of PKC activity (i.e. a constitutive activation and redistribution in the cell nucleus). This process is probably responsible for the diverse effects of lithium on the release of neurotransmitters, the inhibition of receptor sensitization and certain membrane transport processes. By influencing transcription factors such as c-fos, this process could also be responsible for the lithium-induced changes in gene transcription which have been observed.
The inhibitory effects of chronic lithium treatment on the PI system have also been demonstrated in humans. Peripheral cells from manic-depressive patients show increased hormonal sensitivity in the phosphoinositide (PI) system. Thus, it appears that lithium ions might compensate for the hyperactivity of the PI system which is associated with illness in these patients.
back >>
The Effect of Lithium on Serotoninergic Function (B. Müller-Oerlinghausen)
In animal experiments, lithium administration results in a net rise in 5-HT activity, which is probably caused presynaptically by an increase in the release and transformation of 5-HT precursors, an increase in the release of 5-HT, and by the functional antagonism between lithium and inhibitory presynaptic 5-HT1A receptors.
However, there are considerable differences in the amount of time which elapses before each of the different effects occurs.
An increase in 5-HT uptake in the thrombocytes of depressive patients, but not in those of healthy test subjects, has been observed.
In several studies of patients and healthy volunteers on short-term lithium therapy, neuroendocrine stimulation (e.g. with fenfluramine or tryptophan) led to increased prolactine or cortisol responses via serotoninergic transmission.
The presumably adaptive mechanisms which tend to emerge after chronic lithium administration (e.g. a decrease in the number and sensitivity of postsynaptic 5-HT receptors) probably result in a stabilization of serotoninergic neurotransmission rather than a unidirectional increase in 5-HT activity.
back >>
The Effects of Lithium on the Hematopoietic System (V.S. Gallicchio)
Lithium increases the number of neutrophil and eosinophil granulocytes, but probably not that of monocytes, basophil granulocytes, thrombocytes or erythrocytes/reticulocytes in peripheral blood.
Whereas lithium increases the number of pluripotent stem cells in bone marrow, as well as of granulocyte-macrophage and megakaryocyte precursors, it probably reduces the number of erythrocyte progenitor cells.
Researchers suspect that these phenomena result from both the direct and indirect effects of lithium on cells, including an increase in the number of macrophages that produce growth factors and cytokines. A lithium-induced increase in bone marrow activity also appears to play a role in this context. A decline in erythropoiesis during lithium therapy may be due to inhibition of cAMP which, in turn, inhibits prostaglandin E production.
Thus, lithium can be used to treat toxic impairment of the hematopoietic system, whether this damage be caused by chemotherapy, radiation, antiviral medication, or granulocytopenia induced by carbamazepine or neuroleptics.
To date there has been no scientific evidence that lithium can cause leukemia.
back >>
The Effects of Lithium on the Immune System (V.S. Gallicchio)
In humans lithium therapy may lead to an increase in immunoglobulin synthesis by B-lymphocytes. However, the results of in vitro experiments and animal testing are contradictory.
Lithium stimulates the proliferation of T-lymphocytes and appears to increase the phagocytic activity of macrophages, but only at doses higher than those prescribed for medical treatment.
Experimental evidence suggests that lithium can increase cytokine production. This has been confirmed in the case of interleukin-2. Moreover, lithium potentiates tumor necrosis factor-mediated cytotoxicity. In high doses, lithium inhibits cyclic AMP (cAMP), which leads to an increase in the synthesis of interferon products.
It appears that lithium influences the immune system in part by reducing intracellular concentrations of cAMP and inositol phosphate.
Because of the high doses involved, the potential usefulness of lithium in the treatment of inflammatory and auto-immune diseases is still unclear. However, because it can increase interleukin-2 production, as well as potentiate killer cell activity, high-dose lithium has been used in the treatment of various cancers. Recent evidence also indicates that, by inhibiting T-suppressor cells lithium can reduce the severity of graft-versus-host reactions following transplants.
Of great importance is the potential use of lithium in the treatment of immune deficiency syndromes such as AIDS. In vitro experiments have shown that lithium can lead to a more robust immune response in patients with AIDS. The direct antiviral effects of lithium, e.g. in herpes virus infections, are already being utilized in clinical practice.
back >>
Chronobiological Aspects of Lithium Prophylaxis (B. Pflug)
Repetitive variations with a periodicity of approximately 24 hours are part of the circadian system. This system can be found among single-celled organisms, plants, animals, and humans.
In humans the circadian system is based on a number of oscillators of varying strengths which exert mutual influence on one another. The main pacemaker of this multi-oscillatory system is the nucleus suprachiasmaticus.
Lithium ions are chronobiologically active. They influence the circardian system by modifying phase relationships and lengthening the free-running period.
During manic-depressive episodes a variety of circadian rhythm dysfunctions have been observed.
The chronobiological effects of lithium salts help explain their efficacy in the treatment of manic-depressive disorders.
back >>
The Psychological Approach to the Effects of Lithium Prophylaxis (W. Classen)
The main effect of long-term lithium treatment is based on the modification of behavior and perception. These effects can be explained within psychological models and need not be reduced to other, lower levels of explanation.
Over the last 25 years, animal studies, psychophysiological investigations in humans, and routine clinical observation have led to the development of models which help explain the psychological effects of lithium salts. The phenomenological model developed by Kropf integrates concepts of genetic disease, aspects of the illness described in psychological terms, as well as the acute and chronic effects of lithium.
Among healthy test subjects lithium can cause fatigue, apathy, irritability, alternation between increased and decreased susceptibility to external stimuli, and general feelings of illness along with negative thinking, dysphoria, and lethargy.
Depressive patients exhibit a rigid and non-regulable behavioral repertoire, both during acute episodes and over the long term. This indicates a change in mental functions, such as cognition, perception, emotions, and the ability to structure thoughts and process information. Lithium most likely modulates these processes by raising the perception threshold for various stimuli and improving information processing structures.
The aggression-dampening effect of lithium which has been observed in human and animal studies is probably due to changes in the perception of aggression-inducing stimuli, as well as to improved control over aggressive impulses accompanied by a reduction in the number of aggressive behavioral patterns.
back >>
The Pharmacokinetics of Lithium Salts (K. Lehmann)
The kinetics of lithium are determined by the fact that it is a simple, monovalent cation.
The anion and/or the galenic formulation chosen for the final drug product primarily influence the resorption phase. This needs to be taken into account when initiating lithium treatment or changing a patient’s prescription.
The primary route of lithium elimination is renal (via glomerular filtration). Between 70-80% is reabsorbed in the proximal tubule. The overall elimination half-life of lithium is approximately 24 hours.
The exogenous clearance of lithium (ca. 19-20%) is approximately equal to the endogenous clearance of the drug in patients with normal renal function.
The renal clearance of lithium is subject to manifold influences, the most significant of which are (a) changes in electrolyte levels and (b) the secretion of aldosterone.
Impaired kidney function and age-related decreases in renal clearance can lead to a dramatic rise in serum lithium levels.
Lithium is distributed slowly and unevenly in the human body. Distribution is usually complete within 12 hours of first ingestion. During lithium therapy, steady state concentrations are generally reached within 4-7 days of repeated oral application in patients with normal renal function.
Exact drug monitoring is absolutely essential not only in all problem cases or when medication(s) are adjusted or switched, but also during routine follow-up exams.
back >>
Clinical Effects and Indications
Treatment of Acute Mania with Lithium and Other Pharmaceuticals (H.-P. Volz, H. Sauer)
Abstract
Lithium is the medication of choice for patients suffering from mild to moderate mania. There is as well substantial clinical evidence for recommending valproate or olanzapine monotherapy in mild to moderate cases.
Patients suffering from severe or mixed mania who exhibit pronounced motor restlessness and psychotic symptoms should be treated first with lithium plus an atypical antipsychotic or valproate plus an atypical antipsychotic such as olanzapine or risperidone.
If a patient does not respond to first line treatment, combination of two first-line treatments should be considered. If no improvement is seen, clozapine or electro-convulsive therapy may be indicated.
Lithium is less effective for rapid cycling mood disorder and mixed manic-depressive episodes than it is for classical manic syndromes. For mixed episodes valproate may be preferred over lithium. The therapeutic efficacy of lithium is also lower in the context of organic mania.
back >>
Treatment of Acute Depression with Lithium (M. Bauer)
Abstract
The majority of open and controlled studies demonstrate that acute lithium therapy has a clear antidepressive effect, especially among depressive patients with bipolar disorder.
Nevertheless, lithium is widely regarded as a substance with only “moderate antidepressive” efficacy and is not the medication of first choice for the acute treatment of severe depressive illness. This prevailing opinion possibly is related to the narrow therapeutic index of lithium.
However, a number of clinical situations exist in which lithium plays an important role in the acute treatment of depression. These include:
- bipolar patients suffering from a depressive episode of mild to moderate severity. (Bipolar disorder is a good predictor of a positive response to lithium, and the risk that a patient will switch to a manic state is lower when he or she is treated with lithium instead of antidepressants.)
- depressive patients who do not respond to antidepressant monotherapy. (Lithium “augmentation”: the use of lithium as an adjunct to antidepressant monotherapy has been confirmed as an effective means of treating therapy-resistant depression. Between 50-60% of therapy-resistant depressive patients respond to the addition of lithium within 2-6 weeks.)
- patients who switch into mania during treatment with an antidepressant.
- unipolar patients in whom lithium prophylaxis is already indicated due to recurrent depressive episodes.
- patients who, for medical reasons, should not be given antidepressants.
back >>
The Long-term Prophylaxis of Affective Disorders with Lithium (W. Greil, N. Kleindienst)
In the long-term treatment of affective disorders, a distinction is made between maintenance therapy (i.e. the prevention of relapse during a period of illness that is not yet completely resolved) and long-term prophylaxis (i.e. the prevention of future recurrences/episodes of illness). For maintenance therapy, the medication administered during the current acute phase of the manic and/or depressive episode is continued for a period of 4-6 months. For long-term prophylaxis, mood stabilizing substances – primarily lithium and antidepressants, but more recently also anticonvulsants – are used.
Long-term prophylaxis is indicated in cases in which a high frequency of recurrences is to be expected. For example, patients suffering from bipolar affective disorders (with manic and depressive phases) experience recurrences more frequently than patients with unipolar depression (with exclusively depressive phases). The recurrence rate also increases with the number and frequency of previous periods of illness.
Controlled studies comparing long-term lithium treatment to placebo (or to no pharmacotherapy) have yielded conclusive evidence that lithium is effective in preventing relapse of bipolar manic episodes, and strong evidence that lithium can prevent relapse of bipolar depressive episodes. There is also sufficient evidence that long-term lithium therapy can prevent the recurrence of unipolar depressive episodes.
Studies comparing lithium to tricyclic and tetracyclic antidepressants in the long-term prophylactic treatment of unipolar depressive episodes have yielded contradictory results: Most studies show the efficacy of lithium to be the same or greater than that of the tricyclics and tetracyclics. In one study, however, lithium was shown to be less effective. In the context of bipolar disorders, there is not yet enough evidence to determine whether anticonvulsants have the same long-term prophylactic efficacy as lithium.
Studies conducted in special lithium clinics and with adequate treatment monitoring have shown that, when the course of disease before lithium treatment was compared to the time during treatment, between 65% and 80% of patients showed a positive response to therapy. Response to therapy was defined as the absence of relapse (i.e. full response) or the decrease in frequency, severity and/or length of recurrent episodes (i.e. partial response). Treatment failure (i.e. non-response) occurred in 20-35% of patients. Naturalistic studies have shown, however, that the effectiveness of lithium in the prevention of recurrent episodes is lower under routine conditions. “Effectiveness” must not be confused with “efficacy” in this context.
back >>
Prophylaxis of Schizoaffective Psychoses (G. Lenz, B. Bankier)
Abstract
The introduction of the ICD-10 and DSM IV into clinical practice has made the diagnosis of schizoaffective disorders more reliable and valid.
The scientific evidence for prophylactic efficacy of various compounds commonly used in psychiatric practice is poor. The data encourage the use of lithium and carbamazepine in primarily affective patients, and of clozapine in primarily schizophrenic patients and possibly in mainly affective patients as well.
Studies have shown that patients suffering from the schizomanic/affective subtype (according to RDC) respond well to lithium prophylaxis, whereas those with the schizodepressive/schizophrenic subtype do not.
Among patients with the schizomanic subtype (according to RDC), carbamazepine prophylaxis is just as effective as prophylactic lithium therapy. However, some studies show that among patients suffering from the schizodepressive subtype, carbamazepine is clearly superior to lithium in terms of hospitalization and shows a tendency in terms of fewer recurrences.
In the long-term treatment of patients with the schizophrenic subtype (according to RDC), neuroleptics have been shown to be markedly superior to lithium prophylaxis.
Some open studies indicate that valproic acid may also be able to reduce the frequency and intensity of further schizoaffective episodes.
back >>
Selection Criteria for Curative and Prophylactic Lithium Treatment (P. Grof)
When deciding whether a patient will benefit from long-term lithium therapy, it is important to assess the risk of relapse, the psychosocial effects of the disease on the patient, and the general medical risk of lithium treatment.
The recurrence increases with the number and frequency of previous episodes. Although it is possible to accurately predict the course of disease for large groups of patients, doing so for individual patients is difficult due to interindividual variation. In general, the risk of relapse increases with the frequency and number of previous episodes of illness. The risk of relapse is considered high in the following cases: bipolar disease with 2 phases in the previous 4 years, or a total of 3 phases regardless of the time period in which they occur and (b) unipolar disease with 2 phases in the previous 5 years, or a total of 4 phases regardless of the time period in which they occur.
It is important to distinguish between long-term therapy of choice and a limited therapeutic trial. In typical cases of bipolar or unipolar affective disorder, lithium is the long-term therapy of choice when patients experience periods of complete remission and are free of all psychopathological symptoms (i.e. patients with a normal profile according to the MMPI [Minnesota Multiphasic Personality Inventory]).
A family history of bipolar affective disorder increases the chance of a positive response to lithium prophylaxis. However, the occurrence of 4 or more phases in one year decreases, but does not preclude, the chance of a positive response. Lithium therapy can also prevent recurrences in patients suffering from schizoaffective illness or schizophrenia with a periodic course. However, there are no known predictors for these latter two patient groups.
Before deciding in favor of long-term lithium therapy, it is essential to consider carefully the pros and cons of lithium treatment when compared to the other drug regimens currently available.
Manic patients who respond well to acute treatment with lithium are generally those who are suffering from classic manic symptoms. Lithium can be regarded as the therapy of choice in patients who have a history of positive response to acute or prophylactic lithium treatment.
back >>
The Differential Effects of Lithium and Their Significance When Terminating Long-term Lithium Therapy (P. Grof)
There is conflicting information in the literature on the consequences of terminating lithium therapy. This is primarily due to the fact that the risk assessments made so far have not taken into account interindividual variation in the effects of lithium treatment.
Lithium therapy can be terminated immediately and need not be tapered off in patients who have responded very well to lithium prophylaxis and have been completely free of symptoms while on treatment. When recurrences do occur, they tend to develop gradually and over a period of time that can range anywhere from several weeks to several years (i.e. according to the natural course of illness before lithium therapy was first initiated). Usually, patients who experience a recurrence can be stabilized again by reinitiating treatment.
If lithium therapy was initiated primarily because of its antipsychotic effects (i.e. unspecifically), abrupt withdrawal can very quickly lead to a recurrence, most often in the form of a “rebound.” Reinitiation of lithium therapy does not always result in restabilization. In such cases, the dosage of lithium should be reduced gradually.
Patients often interrupt or terminate lithium therapy without consulting their physician. Frequently, this occurs at a point in time when the risk of recurrence is particularly high.
Medical reasons for stopping lithium therapy include non-response to the drug, signs of toxicity and severe side-effects. Lithium treatment should also be terminated prior to certain medical examinations and before pregnancy. However, each patient needs to be examined carefully and advised of the potential risks involved in his or her particular case before the decision to terminate lithium treatment can be made.
back >>
The Anti-suicidal and Mortality-lowering Effects of Lithium (B. Ahrens, B. Müller-Oerlinghausen)
Abstract
Among patients with affective disorders the risk of suicide is anywhere from 20 to 30 times greater – and overall mortality is 2 to 3 times higher – than in the general population.
Lithium has a mortality-lowering effect, as well as specific anti-suicidal properties. The latter are at least partially independent of the episode-preventing effects of lithium in recurrent depressive and bipolar disorder.
When determining the appropriateness of lithium treatment, it is important to consider any history of suicidal behavior in the patient or the patient’s family.
Patients with a history of suicidal behavior can benefit from the anti-suicidal properties of lithium, even if lithium prophylaxis fails to prevent recurrences. In such cases, it is possible to continue lithium as an adjunct to an alternative prophylactic regimen.
The use of lithium prophylaxis prevents an estimated 200 suicides per year in Germany, despite the fact that the prescription rate of lithium is very low (approximately 0.06% of the population) and, by some estimates, should actually be at least ten times greater.
A mortality reducing effect has not been shown convincingly for any other mood stabilizing or antidepressant drug.
back >>
Lithium in the Treatment and Prophylaxis of Pathological Aggression (A. Nilsson)
Systematic research on lithium and pathological aggression conducted in a number of different fields (e.g. studies in adult psychiatry, of children and youths with behavioral disorders, of mentally retarded individuals, and of isolated impulse-control disorders among prisoners) have unanimously shown that the serum lithium levels normally reached in the long-term treatment of bipolar disorders can reduce impulsive aggression.
Scientific investigations of aggression are still plagued by a multitude of methodological problems. There is, for example, still no adequate or uniform definition of aggression. Of particular clinical interest is the pathological overreaction with primarily destructive intent.
The majority of studies on aggression have been conducted in closed institutions. This makes it difficult to devise optimal treatment strategies for outpatient medical care.
The clinical significance of lithium for this indication is minimal. This may be attributable to ethical reservations about prescribing medication to control aggressive behavior, or possibly to problems with compliance in this particular patient population.
back >>
Lithium Salts in Child and Adolescent Psychiatry (G.H. Moll, A. Rothenberger)
For the treatment of a manic episode in childhood or adolescence, lithium salts – like neuroleptics – are the medication of choice. A combination treatment of lithium with neuroleptics is possible, but requires especially careful monitoring.
If a child or adolescent suffering from unipolar depressive episodes does not respond sufficiently to treatment with antidepressants, adding lithium salts during the depressive episode – to increase the effectiveness of overall therapy – and then continuing lithium treatment as long-term prophylaxis can be beneficial. After approximately 3 years, the need for further treatment should be assessed.
For adolescents, as well as adults, lithium salts are considered to be the medication of choice in the long-term prophylactic treatment of bipolar affective disorders. In contrast to the treatment of these disorders in adults, however, the unique developmental conditions which characterize young adulthood make it advisable to begin treatment in adolescents at an early stage, i.e. already during the first episode. In the event of non-response, carbamazepine can be administered as an alternative treatment.
Lithium salts can lead to improvements in patients with strongly pronounced explosive aggressive behavioral disorders, as well as in those who exhibit impulsive, self-destructive behavior (i.e. auto-aggression). Therapy should take place in an inpatient setting for at least the first 6 to 8 weeks of treatment. As is the case with the above mentioned affective disorders, there is only minimal evidence of benefit when carbamazepine is used in this indication.
If pedagogical approaches and behavioral therapy have been unsuccessful, child and adolescent patients with intellectual deficiency and who exhibit explosive aggressive and/or auto-aggressive, self-destructive behavior may benefit from inpatient treatment with lithium salts.
The recommended dosage and serum levels of lithium salts, as well as side-effects and contraindications, are the same in adolescents as they are in adults. However, lithium therapy is currently not recommended for children under the age of 12, unless it is administered on a strictly inpatient basis.
Even when therapy with lithium salts is clearly indicated in child or adolescent patients, it should nevertheless be regarded as only one component of a larger, comprehensive, and multifaceted treatment plan that takes into account each patient’s symptoms, state of development and function, as well as his or her specific psychosocial circumstances.
back >>
Neurological Indications for Lithium Therapy (A. Berghöfer)
The main application of lithium in the field of neurology is as a treatment for chronic cluster headaches.
Lithium is no longer considered for the prophylaxis of migraine headaches due to contradictory evidence regarding its efficacy in this particular context.
The efficacy of lithium in the treatment of other neurological disorders (Meniere’s disease, epilepsy, Huntington’s disease, Parkinson’s disease, tardive dyskinesia, periodic hypersomnia, Gilles de la Tourette's syndrome, spasmodic torticollis, hypokalemic periodic paralysis) has not yet been demonstrated.
In isolated cases, lithium treatment in patients suffering from symptomatic affective psychoses which appeared in the context of a neurological disorder has been reported to be successful.
back >>
The Antiviral Effect of Lithium in the Treatment of Herpes Simplex Infections (J.K. Rybakowski)
Under experimental conditions, lithium inhibits the replication of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) at a concentration of 5-30 mmol/l, most likely by interfering with viral DNA synthesis.
Long-term treatment with lithium at doses typical for the prophylaxis of affective disorders can attenuate or even inhibit the reactivation of labial or genital herpes infections, both in patients with affective psychoses and in individuals who do not suffer from a psychiatric illness.
Topical therapy with 8% lithium succinate ointment has been shown to have a positive therapeutic effect on herpes lesions.
The effect of lithium on herpes infections may not only be due to the inhibition of viral DNA synthesis, but also to the stress-reducing, immunomodulatory, and anti-inflammatory properties of the drug.
back >>
Adverse Effects of Lithium Salts
The Neurological, Neuromuscular, and Neurotoxic Effects of Lithium Treatment (P. Mavrogiorgou, U. Hegerl)
Lithium can cause adverse effects in the central and peripheral nervous system, even at standard therapeutic serum lithium levels.
These include common and relatively harmless side-effects such as lithium-induced tremor and non-specific EEG changes, but also infrequent, though severe, neurotoxic effects such as rigidity, nystagmus, and cognitive impairments.
Risk factors for these severe neurotoxic effects are, above all, pre-existing cerebral abnormalities, advanced age, and combination therapy (especially with neuroleptics).
The neurotoxic effects of lithium are generally reversible and must be treated symptomatically. For cases of lithium-induced tremor in which a reduction in serum lithium levels is insufficient or impossible, propranolol (10-40 mg/day) is now regarded as the therapy of choice.
back >>
Lithium and the Cardiovascular System (J. Albrecht)
ECG repolarization abnormalities during lithium treatment are dose-dependent, reversible, and have no clinical relevance.
Arrhythmias occur only infrequently at therapeutic serum lithium levels. When they do occur, the most predominant changes are in the sinoatrial node function and conduction properties of the atria and atrioventricular node (supra-His), accompanied by replacement rhythms, or extrasystoles.
From a pathophysiological viewpoint, these abnormalities appear to result from a increase in action potential duration with a concurrent increase in refractory time, as well as a decline in the rate of depolarization (phase 4 depolarization).
Because of the risk of syncopal attacks, relative contraindications to lithium therapy include disorders that involve sinus node dysfunction and bradyarrhythmias.
back >>
The Effects of Lithium on Thyroid Function (T. Bschor, M. Bauer, J. Albrecht)
Lithium is a thyrostatic substance that decreases the synthesis of thyroid hormones. The body compensates for this deficit by producing more TSH which, however, also promotes euthyroid goiter formation.
Recent sonographic studies have been conducted in Germany on the frequency of goiter formation during lithium treatment show that the prevalence is probably much higher than previously thought (i.e. above 50%). Lithium-induced goiters are, however, only of moderate size (grade 1).
Approximately 10-20% of patients on lithium treatment have latent/subclinical hypothyroidism (i.e. a greater than normal increase in TSH production).
Clinical manifestations of hypothyroidism occur much less frequently than latent hypothyroidism. When they do occur, they do so more frequently in women and are often the result of a lithium-induced auto-immune reaction. Autoantibodies directed against thyroid tissue (i.e. against thyreoglobuline and microsomes) are elevated in patients with affective disorders and who are on lithium treatment, although this is not necessarily a clinical sign of thyroiditis.
Isolated cases of hyperthyroidism in patients taking lithium have been reported.
back >>
Lithium and Kidney Function (D. Kampf)
The renal side-effects of lithium primarily affect the tubulo-interstitium, but occasionally also the glomerular apparatus. It is absolutely essential to differentiate between the effects of an adequately monitored lithium therapy and lithium intoxication. Many publications fail to make a careful and accurate distinction between the two conditions.
Approximately 25% of patients on medium-term lithium therapy (<15 years), as well as most patients on long-term lithium treatment (>15 years), develop chronic lithium nephropathy. The primary clinical manifestation of this condition is impaired urinary concentration, which may or may not be accompanied by polyuria. This loss of function is of little clinical relevance. However, patients with severe polyuria are at a greater risk of experiencing lithium intoxication as a result of fluctuations in sodium levels. The glomerular filtration rate remains stable in most patients, even during long-term lithium therapy. Morphologically, the condition presents as largely unspecific, chronic interstitial nephropathy.
Lithium intoxication, on the other hand, can lead to a drop in the glomerular filtration rate and, ultimately, to acute oligoanuric renal failure. Morphologically, the renal effects of lithium intoxication range from minor tubular changes to acute tubular necrosis. Reducing or removing excess amounts of lithium generally leads to a full recovery. Recurrent lithium intoxication, however, appears to promote the development of progressive lithium nephropathy. Because of this, it is absolutely essential to monitor serum lithium levels regularly. Subclinical lithium intoxication should also be avoided.
A very infrequent side-effect of lithium prophylaxis is nephrotic syndrome, which presents morphologically as a minimal lesion or, less frequently, as focal segmental glomerular sclerosis. Discontinuing lithium treatment generally results in full remission of the minimal lesion, whereas restarting lithium therapy usually leads to a rapid relapse.
In isolated cases, lithium has been shown to impair renal tubular acidification by way of incomplete distal renal tubular acidosis. However, this impairment is not accompanied by systemic acidosis and thus has no clinical relevance.
back >>
The Effects of Lithium Salts on Carbohydrate Metabolism, Body Weight, and Gastro-intestinal Functions (B. Müller-Oerlinghausen)
Under certain experimental conditions, and particularly in animal experiments, lithium can exhibit insulin-like effects. However, the insulin-induced release of glucose may also be inhibited.
A number of researchers have conducted glucose tolerance tests on patients receiving long-term lithium therapy. These tests have yielded contradictory results. An impairment in glucose tolerance is most likely attributable to a lithium-induced increase in body weight.
Weight increase appears to occur in one-third of patients on lithium therapy, these patients gaining between 4 and 10 kg on the average. Eating behavior typical of overweight individuals, as well as the consumption of high caloric drinks, play an important role in this regard.
Excess mortality due to cardiovascular disease is a well-known effect of manic-depressive disorders. As a result, excessive weight gain in this patient group should be prevented as early as possible.
Nausea, abdominal pains and frequent bowel movements are common side-effects of lithium treatment. Their intensity and frequency are dependent on the type of drug formulation used. The timing of drug intake (i.e. before or after a meal) also plays an important role in this context.
back >>
Dermatological Side-effects of Lithium Therapy (G. Albrecht)
Dermatological side-effects of lithium are rare.
Lithium can trigger adverse skin reactions, exacerbate pre-existing dermatoses and/or cause resistance to certain dermatological treatments.
Lithium therapy can trigger a first outbreak of psoriasis, aggravate pre-existing psoriasis or cause patients to develop the pustular form of the disease. However, lithium succinate can be used topically to treat seborrhoic eczema.
Acne and acneiform dermatoses are the most commonly described skin conditions associated with long-term lithium therapy. They appear more frequently in younger patients. Lithium has a stimulating effect on neutrophil granulocytes, which in turn appears to promote the development of pustular diseases.
Patients suffering from the more common, milder skin reactions should be treated according to standard dermatological procedure. If the dermatosis, however, is more extensive and/or causes the patient great distress, a reduction in the dose of lithium should be considered. Terminating lithium therapy is only necessary in exceptional cases.
back >>
Lithium-induced Endocrine Changes (J. Schleicher, D. Kampf)
Between 10-42% of patients on lithium therapy develop hypercalcemia, and up to 29% develop hyperparathyroidism. Possible causes are increased secretion of intact parathormone (iPTH), a decrease in parathyroid sensitivity to calcium, or cell hyperplasia of the parathyroid gland. Monitoring serum calcium levels before and during lithium therapy is obligatory.
To date there is no evidence that endocrine hypertension can be provoked by lithium treatment. Nevertheless, blood pressure checks are an important part of therapy monitoring.
Lithium can reduce testosterone levels, especially in older men. An increase in luteinizing hormone (LH) may indicate that Leydig cell function is impaired. Prolactin levels remain unchanged during lithium treatment. As of yet, the influence of lithium on female sex hormones has not been sufficiently studied.
Among patients on lithium therapy, no clinically relevant changes have been observed in levels of growth hormone, anti-diuretic hormone (ADH), the renin-angiotensin system, aldosterone, adrenocorticotropic hormone (ACTH), cortisol, or melatonin.
back >>
The Effects of Lithium on Pregnancy and Sexuality (A. Berghöfer)
Animal experiments have shown that lithium leads to abnormal embryonic development only when the dam has received a toxic or lethal dose of the drug.
Today, researchers and physicians are no longer certain that the risk of abnormal fetal development is higher than normal during lithium therapy in human mothers (at standard serum lithium concentrations). To date lithium has not been shown to have mutagenic effects.
The side-effects of lithium therapy apply both to the pregnant mother and the embryo. However, the toxicity threshold for the fetus is lower.
Because of this, it is absolutely essential that physicians give their patients clear and detailed information about the benefits and risks of lithium therapy during pregnancy so that these can then be carefully weighed. The pregnancy itself must be monitored closely and, if at all possible, by a specialized team of experienced physicians and nurses. Serum lithium levels need to be low and consistent, and should be monitored every two weeks. The fetus should also be examined regularly via ultrasound, including echocardiogram.
Switching from lithium therapy to an antiepileptic for prophylactic treatment is not an alternative, as current evidence indicates that carbamazepine and valproate carry with them a significantly higher risk of teratogenicity.
A mother may nurse her child when on lithium therapy. However, the child’s development must be properly monitored and the advantages of breastfeeding over formula-feeding need to be weighed against the risks.
Changes in the sexual behavior of patients on lithium have been reported, especially with regard to libido, potency, and male erection. Such effects are plausible considering lithium’s mechanisms of action and must be carefully differentiated from changes caused by the patient’s primary illness.
back >>
Lithium Intoxication (W.P. Kaschka)
Lithium intoxication can manifest itself in a number of ways, including central nervous, neuromuscular, gastrointestinal, cardiovascular, renal, and other, less frequent groups of symptoms.
There is, at best, a rough correlation between serum lithium levels and the symptoms of lithium intoxication. As an approximate guide for clinical practice, it can assumed that serum lithium levels of 1.5 mmol/l or more will generally lead to adverse side-effects. Clear signs of lithium intoxication can almost always be observed at serum lithium levels of 2.0 mmol/l or more. Levels of 3.5 mmol/l or more can result in death.
Lithium intoxication cannot be ruled out simply based on the fact that serum lithium levels are within therapeutic limits. If in doubt, it can be helpful to determine the lithium concentration in brain tissue using NMR spectroscopy. Alternatively, it is possible to measure the concentration of lithium in erythrocytes.
The risk of permanent organ damage, especially of the brain and kidneys, increases with the time the body is exposed to toxic concentrations of lithium. Therefore, if a patient is diagnosed with lithium intoxication, it is important to act immediately.
Lithium intoxication can be caused either by a single, large overdose of lithium salts (i.e. as part of a suicide attempt) or a reduction of renal lithium clearance resulting, for example, from kidney disease. Because renal function can be influenced by a variety of factors, it is absolutely essential that physicians be aware of anything that might predispose their individual patients to lithium poisoning.
Physicians who administer lithium prophylaxis must be well-trained in pharmacology, have experience with the administration and monitoring of long-term lithium treatment, and be able to build a relationship of mutual trust between themselves, their patient, and – if possible – people who are part of the patient’s psychosocial environment.
back >>
Treatment of Lithium Intoxication (T.R. Zilker)
Lithium has a high volume of distribution, a long plasma elimination half-life, and – though the drug is cleared primarily by the kidneys – minimal renal clearance. This unfavorable pharmacokinetic profile makes it difficult to treat lithium poisoning.
Lithium poisoning is treated on a primarily symptomatic basis. Gastric lavage or induced emesis are only helpful in the event of acute overdose (e.g. from a suicide attempt) and if performed within one hour of drug ingestion. Most often lithium has already been absorbed and it is necessary to enhance the excretion of lithium from the body. This can be accomplished using several methods, including saline infusion, fluid therapy while ensuring that kidney function is maintained, and – in the event of severe intoxication – hemodialysis.
The goal of symptomatic treatment is to maintain adequate respiration, stop any cramping which may occur, treat arrhythmias, and restore fluid and electrolyte balance. Cardiovascular-stimulating drugs have to be used in patients exhibiting signs of shock. Changes in thyroid function and the hematopoietic system must be monitored and, if necessary, treated.
In mild cases of lithium intoxication with sodium loss, clearance of lithium can be increased by administering sodium chloride. Severe cases, however, require one or more hemodialysis sessions. The interval between two sessions can be bridged using hemofiltration.
The best form of treatment is determined by the overall clinical picture, serum lithium concentration, and the state of renal function. Comatose patients should undergo immediate hemodialysis. Depending on their general condition, patients with neurological symptoms, but without disturbance of consciousness, should be kept in intensive care and treated symptomatically. If, however, a patient’s serum lithium level is above 3 mmol/l, or if it is above 2 mmol/l and his or her general condition is poor, then he or she should undergo hemodialysis.
back >>
Interactions Between Lithium Salts and Other Drugs (B. Müller-Oerlinghausen)
Due to older age, multimorbidity, treatment by different doctors, self-medication, and recurrent episodes of illness, it is common for patients on long-term lithium therapy to be concurrently taking one or more drugs in addition to lithium.
Of the psychotropic drugs which can be administered concurrently with lithium, neuroleptics such as haloperidol or thioridazine are those which most commonly lead to clinically relevant side-effects, even if the absolute number of cases is quite low overall. When side-effects do occur, however, it is important to make a clear distinction between the neurotoxic effects that can arise when serum lithium is at therapeutic levels and the side-effects which result from high doses of neuroleptics and/or subtoxic serum lithium concentrations. In certain cases, antidepressant drugs – especially SSRIs – taken together with lithium salts can induce serotonin syndrome.
Antiphlogistics, such as diclofenac, ibuprofen, indomethacine, piroxicam, but not acetylsalicylic acid or sulindac, reduce renal lithium clearance and thus increase the risk of lithium intoxication.
The same applies to diuretic medications, which are often used to treat high blood pressure. Thiazide diuretics appear to be the strongest inhibitors of renal clearance. Potassium-sparing substances have the lowest inhibitory potential with regard to lithium clearance. Furosemide appears to be relatively safe when administered to patients on long-term lithium therapy, but only in the absence of dehydration. Both methyldopa and, above all, ACE inhibitors can induce lithium intoxication.
Lithium should be stopped 24-48 hours prior to surgical procedures or electroconvulsive therapy. In some patients, lithium may increase the severity of ECT side-effects and prolong the neuromuscular blockade caused by muscle relaxants.
back >>
The Pharmacoeconomics of Lithium Prophylaxis (K. Lehmann, B. Ahrens, B. Müller-Oerlinghausen)
A recent critical analysis of the pharmacoeconomics of long-term lithium prophylaxis showed that the benefits of such treatment clearly outweigh the costs.
In Germany, the prescription volume for lithium in 1991 amounted to at least 16 million defined daily doses. Treatment frequency in the German population was approximately 0.06%.
The yearly cost of long-term lithium treatment was estimated at Euro 444 per patient.
In 1991, lithium prophylaxis in the Federal Republic of Germany resulted in a savings in the gross national product of approximately Euro 113 million.
Long-term lithium prophylaxis can reduce suicide mortality, leading to a gain of approximately 3060 working years in the population under 65 years of age.
Given the impressive benefits of long-term lithium prophylaxis, it is unfortunate that many patients whose condition clearly warrants treatment are denied adequate prophylactic treatment with lithium.
back >>
Alternatives and Supplements to Lithium Treatment
Prophylactic Efficacy of Antidepressants (B. Woggon)
Abstract
The prophylactic efficacy of antidepressants in the treatment of unipolar affective disorder (i.e. recurrent depression) has been demonstrated in placebo-controlled studies.
Independently conducted meta-analyses of long-term placebo-controlled studies investigating the use of lithium and antidepressants in the long-term treatment of unipolar depression have shown both to have comparable efficacy.
Lithium prophylaxis might be preferable to antidepressants in the treatment of unipolar affective disorder because of better tolerability, superior mood stabilization, increased chances of remission, more potent anti-suicidal properties, and the common difficulty of distinguishing between unipolar or bipolar disease in an initial diagnosis.
According to international guidelines antidepressant monotherapy is not recommended in bipolar depression.
back >>
Long-term Prophylaxis With Anticonvulsants (H.M. Emrich, D.E. Dietrich)
Abstract
The use of anticonvulsants in the long-term treatment of affective psychoses represents an important alternative (or addition) to lithium prophylaxis for patients who do not respond sufficiently to lithium monotherapy, or who cannot be treated with lithium due to side-effects or contraindications.
Studies have shown that carbamazepine and valproate (dipropylacetamid), and possibly oxcarbazepine can be effective in the long-term treatment of affective psychoses. Individually, these drugs can be used in long-term prophylaxis either as adjuncts to lithium therapy or as monotherapeutic agents. In the long-term treatment of affective psychoses, the antimanic potential of these agents is apparently stronger than their antidepressive effects.
Valproate has not been approved for long-term treatment of affective disorders due to the lack of substantial evidence. Valproate therefore can only be recommended as alternative treatment in therapy-refractory courses of illness or in case of adverse effects of first line treatment.
Benzodiazepines have no clinical relevance with regard to long-term prophylaxis, but do appear to be useful in the acute phase to help bridge the time until a stable state has been reached.
back >>
The MAP Study: Long-term Prophylaxis of Affective and Schizoaffective Disorders (W. Greil, N. Erazo)
The MAP study (Multicenter Study Affective Psychoses) was a prospective, controlled pharmacotherapy trial conducted at nine university centers in Germany and with a treatment period of 2 _ years. In this trial, researchers compared (a) the efficacy of lithium and amitriptyline in the long-term treatment of patients suffering from unipolar depression and (b) the efficacy of lithium and carbamazepine in the long-term treatment of patients suffering from bipolar or schizoaffective psychoses.
The carefully documented recruitment process for the MAP trial ensured the representativeness of the 315-patient random sample that was studied. It can therefore be safely assumed that the results cited here can be generalized and applied to patients who are hospitalized due to affective or schizoaffective disorders, and are in need of, and willing to receive, long-term prophylactic treatment.
The comparison of 40 unipolar patients on lithium therapy to 41 on amitriptyline showed lithium treatment to be more effective in terms of the outcome criterion “recurrence or subclinical recurrence.”
The comparison of 74 bipolar patients on lithium therapy to 70 patients taking carbamazepine showed lithium to be either tendentially or significantly superior in all outcome criteria. Among the 90 patients with schizoaffective disorder (43 on lithium; 47 on carbamazepine), differences (in favor of carbamazepine) were only visible in diagnostic subgroups.
More patients on carbamazepine (13) than on lithium (5) had to stop therapy due to severe side-effects. However, the long-term tolerability of carbamazepine was superior to that of lithium.
back >>
Pharmacotherapy of Prophylaxis-resistant Affective Disorders (M. Bauer)
Approximately 20-30% of patients with affective psychoses do not respond adequately to lithium prophylaxis. Particularly challenging from a therapeutic point of view are patients who have suffered more than four affective phases in the previous 12 months (i.e. rapid cyclers).
The term “prophylaxis resistance” has yet to be defined precisely in the literature. A widely accepted and pragmatic clinical definition is non-response to at least two different, properly conducted attempts at treatment (i.e. each >6 months in length and with adequate serum levels of the respective prophylactic agent).
Before choosing a prophylactic regimen other than lithium monotherapy, physicians should first rule out a pseudo-resistance to prophylaxis and optimize lithium therapy.
To date there have been no controlled studies of treatment strategies for prophylaxis-resistant patients. Physicians must therefore base their decisions on case series, open trials, and empirical experience. The best-established treatment method in such patients is combination treatment with lithium and carbamazepine, or lithium and valproate.
A promising new treatment method in the maintenance therapy of prophylaxis-resistant affective disorders is the adjunctive use of supraphysiological doses of L-thyroxine (T4). However, this method is still experimental and requires further examination in controlled studies.
Other therapeutic methods include the adjunctive use of a neuroleptic (e.g. clozapine) to treat bipolar I disorder with primarily manic episodes, as well as the use of an antidepressant to treat patients with unipolar depression or bipolar II disorder. Tricyclics should be avoided in patients who experience rapid cycling, however. Newer methods include treatment with calcium antagonists, the antiepileptic drug lamotrigine, or electroconvulsive maintenance therapy.
back >>
The Role of Cognitive-behavioral Therapy in Lithium Prophylaxis (T. Wolf)
Cognitive variables, such as negative self-assessments, are discussed in the literature as long-lasting vulnerability factors that can result from depressive syndromes and be successfully treated by means of behavioral therapy.
To date, little attention has been paid to the role of dysfunctional cognitive structures in manic-depressive disorders, as these structures appear to be less conspicuous in patients with bipolar disorders during symptom-free intervals than they do in unipolar depressive patients.
Recent studies have shown that manic-depressive patients who have achieved full remission of symptoms may still exhibit dysfunctional cognitive structures despite successful long-term prophylactic treatment. Thus, cognitive-behavioral therapy would also appear to be indicated in this patient group to reduce the risk of recurrence.
back >>
The Role of “Interpersonal and Social Rhythm Therapy” in the Long-term Prophylactic Treatment of Bipolar Disorders (E. Schramm)
In light of the limited efficacy of pharmacotherapy in the treatment of bipolar disorder, as well as the growing awareness of the negative psychosocial effects of the disease, the adjunctive use of psychotherapy appears to be a valid therapeutic option.
“Interpersonal and Social Rhythm Therapy” (IP/SRT) is a version of Klerman and Weissman’s “Interpersonal Psychotherapy” (IPT) specially modified for the prophylactic treatment of bipolar disorders. IPT is among the most effective psychological treatments for depression.
As part of IP/SRT, elements of interpersonal therapy are combined with behavioral therapy in order to help stabilize a patient’s social rhythms. This is based in part on the assumption that mood stability is to a great extent dependent on the regularity of social rhythms and their influence on the stability of biologically-based circadian patterns.
The main objectives of IP/SRT include helping patients cope with the residual symptoms of their disorder, as well with the psychosocial consequences and adverse interpersonal effects of past affective episodes. Other objectives include regulating everyday living patterns and reducing the risk of recurrence. The therapy itself is highly structured and its individual components are clearly outlined in a physician’s handbook.
back >>
Psychodynamic Processes During Long-term Lithium Therapy (U. Rüger)
Long-term lithium therapy reduces a patient’s vulnerability to internal ambivalence conflicts, helping ensure that he or she is able to maintain a moderate (neurotic) functional level without regressing to a low (psychotic) functional level during periods of mental stress.
During long-term lithium therapy it is possible to achieve lasting and dynamic changes in a patient’s family and social surroundings. These changes are due to a reduction in the number of illness episodes, as well as to the patient’s ability to maintain a moderate functional level and thus to process conflicts in a more mature manner. Psychosocial modifications of conflict and relationship patterns are the inevitable result.
Some patients on long-term lithium therapy can benefit from ancillary psychotherapeutic treatment. Adding psychotherapy may be necessary, on the one hand, to help a patient deal with psychosocial conflicts caused by the familial and social changes mentioned above (cf. 2). On the other hand, it may be desirable to employ psychotherapy to treat the intrapsychic pathogenic structures which are partially responsible for the underlying disease.
Family or partner therapy may be indicated in cases in which the family equilibrium has been disrupted in a lasting manner. On a case-by-case basis it may be necessary for another family member to receive psychotherapeutic treatment.
The often long-term nature of lithium therapy makes dealing with the threshold situations that come with advancing age a virtual inevitability. These situations tend to develop their own dynamics and need to be regarded as a threat to the state of equilibrium a patient may initially have reached in his or her life.
back >>
Cooperation Between Doctors, Patients, and Relatives (M. Schou)
Effective lithium prophylaxis requires close cooperation between doctors, patients, and patients’ relatives. It is important for patients to adhere strictly to their medical instructions, and for doctors to pay close attention to any psychiatric problems which may arise during long-term lithium therapy and/or as a result of the underlying manic-depressive disorder.
The advantages of efficient long-term lithium treatment outweigh the disadvantages. Nevertheless, difficulties may still arise, and anticipating these difficulties is the best way to avoid non-compliance and prevent patients from discontinuing therapy against their physicians’ recommendations. Such difficulties arise either because treatment is effective (i.e. eliminates hypomanic phases), or because it is not sufficiently effective. Patients may, for example, resist being “dependent” on a particular medication or therapy. Somatic and psychiatric side-effects can also lead to treatment difficulties. Patients’ interactions with family and friends should also be taken into account.
A loss of creativity and productivity is often attributed to lithium therapy. A study of creativity in artists receiving lithium prophylaxis revealed that some patients experienced a reduction in creative abilities, others experienced no change, and still others experienced an increase. This last group was the largest of the three.
It is important for patients on long-term lithium therapy to know that their physicians can be easily reached if any problems should develop. Nurses, psychologists, and social workers also represent an important source of encouragement and support. In addition, exchanging experiences with other lithium patients can be of great value.
back >>
Laboratory Methods for Monitoring Serum Lithium Levels (N.J. Birch)
In clinical laboratories, lithium can be determined by flame emission spectroscopy (FES) or atom absorption spectroscopy (AAS). The latter of these is more precise and represents the reference assay method. However, FES is cost-efficient and the method used in most laboratories.
Lithium ion selective electrodes (Li-ISE) have recently become affordable and allow for the rapid determination of serum lithium levels while the patient is present. This results in better therapy compliance, as the patient experiences the treatment process in a more immediate and visual manner. The rapid feedback offers both the patient and the physician a number of advantages.
Texts were translated by Matthew D. Gaskins from:
Die Lithiumtherapie – Nutzen, Risiken, Alternativen. 2nd Edition. Müller-Oerlinghausen B, Greil W, Berghöfer A (Eds.) Springer Berlin, Heidelberg, New York 1997
top >>
|
