Unipolar depression lithium

Although there are continuation and maintenance guidelines for the use of antidepressants for unipolar depression, it is not clear how long a patient with bipolar depression should be treated with these medications. Rates of recurrence of bipolar depression of approximately 60% have been observed in patients taking adequate doses of lithium, alone or in combination with imipramine (APA, 1994b). As the TCAs have not been shown to be efficacious for youth with... 

The treatment of the major depressive disorders such as unipolar and bipolar depressions was initially considered to be uniform, ffowever, with psychopharmacological advances, it has been demonstrated that the patients with bipolar depression may be partially responsive, at least prophylactically responsive, to lithium therapy, whereas the patients with unipolar depression are not as responsive (Abou-Saleh 1992). In addition, the treatment of depression may contribute through serendipity to the confirmation of a subgroup of patients with a bipolar disorder referred to as bipolar II. These patients, following treatment with antidepressants, will switch over to a hypomanic or fully manic phase resulting from pharmacological mechanisms. Thus, another subgroup of the bipolar disorder may be identified in the future. 

Consensus Development Panel 1985] confirmed that lithium salts were efficacious and should especially be considered for those considered unipolar but with a family history of bipolar disorder, because perhaps as many as 15% of patients with unipolar depression do subsequently experience hypomania or mania. Lithium may be the ideal maintenance agent for such uncertain patients for whom there is concern that administration of antidepressants may precipitate highs or increase the frequency of cycling and for those who dislike side effects of some antidepressant groups. 

Glen AIM, Johnson AL, Shepherd M Continuation therapy with lithium and amitriptyline in unipolar depressive illness a randomized double-blind controlled trial. Psychol Med 14 37-50, 1984... 

Song F, Freemantle N, Sheldon TA Selective serotonin reuptake inhibitors meta-analysis of efficacy and acceptabihty. BMJ 306(6879) 683-687, 1993 Song L, Jope R Chronic lithium treatment impairs phosphatidylinositol hydrolysis in membranes from rat brain regions. J Neurochem 58 2200-2206, 1992 Souza EG, Mander AJ, Goodwin GM The efficacy of lithium in prophylaxis of unipolar depression evidenced from its discontinuation. Br J Psychiatry 157 718-722, 1990... 

Lithium has been proven effective for acute and prophylactic treatment of both manic and depressive episodes in patients with bipolar illness (American Psychiatric Association 2002). However, patients with rapid-cycling bipolar disorder (i.e., patients who experience four or more mood disorder episodes per year) have been reported to respond less well to lithium treatment (Dunner and Fieve 1974 Prien et al. 1984 Wehr et al. 1988). Lithium is also effective in preventing future depressive episodes in patients with recurrent unipolar depressive disorder (American Psychiatric Association 2002) and as an adjunct to antidepressant therapy in depressed patients whose illness is partially refractory to treatment with antidepressants alone (discussed in Chapter 2). Furthermore, hthium may be useful in maintaining remission of depressive disorders after electroconvulsive therapy (Coppen et al. 1981 Sackeim et al. 2001). Lithium also has been used effectively in some cases of aggression and behavioral dyscontrol. 

A common mistake is to treat bipolar depression in the same manner that one treats unipolar depression, overlooking the need for a mood stabilizer. In bipolar depression, the first pharmacological intervention should be to start or optimize treatment with a mood stabilizer rather than to start administering an antidepressant medication. In addition, thyroid function should be evaluated, particularly if the patient is taking lithium. Subclinical hypothyroidism, manifested as an increased thyroid-stimulating hormone level and normal triiodothyronine and thyroxine levels, may present as depression in affectively predisposed individuals. In such cases, the addition of thyroid hormones may be beneficial, even if there is no other evidence of hypothyroidism. 

In bipolar depressed patients, lithium (with or without concurrent antidepressants) is the maintenance treatment of choice, with divalproex (DVPX) or carbamazepine as potential alternatives (see also Chapter 10, Maintenance/Prophylaxis ). Maintenance lithium has also been shown to prevent relapse in recurrent unipolar depression (Table 7-22). 

TABLE 7-22. Lithium versus placebo maintenance therapy (recurrent unipolar depression)... 

An earlier study of 40 unipolar depressed patients by this same group found a cumulative probability of recurrence over 2 years to be 0.08 with lithium and 0.58 without lithium (290). These investigators concluded that the outcome strongly supported the value of lithium prophylaxis in unipolar depression, contrasting this agent s lack of acute efficacy. 

Souza FGM, Goodwin GM. Lithium treatment and prophylaxis in unipolar depression a meta-analysis. Br J Psychiatry 1991 158 666-675. 

Souza FGM, Mander AJ, Goodwin GM. The efficacy of lithium in prophylaxis of unipolar depression evidence from its discontinuation. Br J Psychiatry 1990 157 718-722. 

An interesting application of lithium that is relatively well supported by controlled studies is as an adjunct to tricyclic antidepressants and selective serotonin reuptake inhibitors in patients with unipolar depression who do not respond fully to monotherapy with the antidepressant. For this application, concentrations of lithium at the lower end of the recommended range for manic-depressive illness appear to be adequate. 

The mood stabilizer lithium was developed as the first treatment for bipolar disorder. It has definitely modified the long-term outcome of bipolar disorder because it not only treats acute episodes of mania, but it is the first psychotropic drug proven to have a prophylactic effect in preventing future episodes of illness. Lithium even treats depression in bipolar patients, although it is not so clear that it is a powerful antidepressant for unipolar depression. Nevertheless, it is used to augment antidepressants for treating resistant cases of unipolar depression. 

Hypothalamic-pituitary-adrenal axis function in bipolar disorder has been reviewed, but lithium was mentioned only in passing (617). Two studies (n = 25, n = 24), possibly reporting many of the same patients, showed that lithium augmentation of antidepressant-resistant unipolar depression increased hypothalamic-pituitary-adrenal axis activity, measured by the dexamethasone suppression test, either alone or combined with the corticotropin releasing hormone test (618,619). However, the tests did not distinguish between lithium responders and nonresponders. 

Affective disorders such as depression and manic-depression are found frequently in the general population as well as in rehabilitation patients. Drugs commonly prescribed in the treatment of (unipolar) depression include the tricyclics and MAO inhibitors as well as the newer second-generation antidepressants. Lithium is the drug of choice for treating bipolar disorder, or manic-depression. All of these drugs... 

Lee W, Cleare A. Lithium augmentation in treatment-refractory unipolar depression. Br J Psychiatry 2003 182 456-7. 

Lithium is one of the most useful adjunctive agents to augment antidepressants for treatment-resistant unipolar depression... 

While there has been a great deal of success in treating manic-depressive patients with lithium and returning them to a normal life, researchers are not exactly sure how it works. It is a non-addictive and non-sedating medication, but its use must be carefully monitored for possibly dangerous side effects. For some patients suffering from some symptoms of schizophrenia, lithium may be used in combination with other medications. Lithium is also used to treat people who suffer from unipolar depression. 

Recent extensive reviews describe current indications for lithium therapy primarily in bipolar disorders and experimentally in unipolar depression as well as schizo-affective schizophrenia, alcoholism, premenstrual cramps and character disorders. These reports also call attention to the narrow therapeutic index associated with its use and the need for careful moniterlng of serum levels. Serum levels of 0.6 to 1.5 mEq per liter are usually sufficient for management of symptoms. A dose of 300mg of lithium carbonate t.i.d. or q.l.d. is recommended to maintain these... 

I Lithium is also used in the prophylaxis of recurrent unipolar depressive disorder. I Controlled trials suggest response rates of 30-40%, and while the strategy is significantly more efficacious than placebo, the magnitude of effect is small. 

By the late 1960s, lithium became the drug of choice for treatment of manic depression. Today, lithium is one of the most reliable drugs for lowering the manic high of bipolar depression. Lithium has proved an efficient treatment for mania with a response rate of 60 percent to 80 percent in classic euphoric mania cases. It is also sometimes used in treatment-resistant unipolar depression. Lithium is commonly taken as a salt, lithium carbonate, and is sold under a variety of brand names (Carbolith, Cibalith-S, Duralith, Eskalith , Lithane, Lithizine, Lithobid). Not only is it unique for calming the manic phase of depression, its chemical structure and properties are like no other antidepressant. 

Antidepressants commonly used for unipolar depression are also effective in treating the depressive stage of bipolar disorder. Often antidepressants such as SSRIs are prescribed in conjunction with lithium to stave off manic highs as well as depressive lows. 

Lithium is used for the prophylactic control of mania and hypomania and bipolar depression. It also has a use in unipolar depression that is unresponsive to other antidepressants. 

In addition, it exerts beneficial effects in many disorders as an adjuvant to other treatment modalities. Such effects are apparent only if it is administered to an already pharmacologically treated patient. For example, in unresponsive major depressive disorder, the co-administration of lithium to an ongoing antidepressant treatment increases the response rate by up to 50%. In most cases, the response to lithium augmentation is either considerable or not at all ( all-or-none phenomenon). Some (currently not convincing) results have also been reported in unipolar depression, bulimia nervosa, and attention deficit hyperactivity disorder (ADHD). Lithium also exerts antiaggressive effects in conduct disorder, independent of any mood disorder, and can reduce behavioral dyscontrol and self-mutilation in mentally retarded patients. One of the most striking effects of lithium is its antisuicidal effect in patients who suffer from bipolar and unipolar depressive disorder irrespective of comorbid axis I disorder. ... 

Unipolar depression In an open randomized study in 46 subjects with unipolar depression examined over 3 weeks lithium augmented mirtazapine successfully (n — 13), but carbamazepine was ineffective when added to mirtazapine (n = 10) compared with mirtazapine alone (n = 23) [14 f. Lithium augmentation in treatment-resistant depression remains among the best studied successful interventions [15 f. 

Schille C, Baghai TC, Eser D, Nothdurfter C, Rupprecht R. Lithium but not carbamazepine augments antidepressant efficacy of mirtazapine in unipolar depression an open-label study. World J Biol Psychiatry 2009 10 390-9. 

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