Trazodone  Trazodone is a second line agent for treatment of depression. Antidepressant effects take several weeks to develop.Trazodone produces selective blockade of serotonin reuptake and may also stimulate serotonin receptor directly.

 Common side effects are sedation, orthostatic hypotension, dry mouth, and nausea. In contrast to the tricyclic agents, trazodone has minimal anticholinergic actions and is not cardiotoxic. Accordingly, trazodone may be useful for elderly patients and other individuals for whom the cardiac and anticholinergic effects of the tricyclics may be intolerable.

Amoxapine is chemicly related to the antipsychotic agent loxapine, and has both antidepressant and neuroleptic properties. Anidepressant effects are equivalent to those of the tricyclics. Because it can cause serious side effects, amoxapine should be reserved for patients with psychotic depression.

 Anticholinergic, sedative effects.  Following overdose, the risk of seizures is greater than with tricyclics. Caution should be exercised in patients with epilepsy. It can block receptors for dopamine. As a result the drug can cause extrapyramidal side effect

 Bipolar disorder is a cyclic disorder characterized by recurrent fluctuation in mood. Typically, patients experience alternating episodes of mania and depression separated by periods in which mood is normal.

 Lithium  Lithium is a simple inorganic ion that carries a single positive charge.  In the periodic table of elements, lithium fall within the same group as potassium and sodium. Accordingly, lithium has properties in common with these 2 elements.  The mainstay of therapy is lithium. Lithium can provide symptomatic control during both the manic phase and the depress phase. In addition, when taken prophylactically, lithium can reduce the frequency and severity of recurrent mania and depressive episodes.

 When used for initial control of acute mania, lithium is usually combined with abenzodiazepine or an antipsychotic agent. These drugs help suppress symptoms until lithium takes effect. Once lithium has taken effect in about 2 weeks, the benzodiazepine or antipsychotic should be gradually withdrawn.  When used during the depressive phase, lithium can be combined with an antidepressant. Options include a tricyclic antidepressant.

The mode of action is unknown. Note: Lithium is believed to attenuate signaling via receptors coupled to the phosphatidylinositol bisphosphate (PIP2) second-messenger system. Lithium interferes with the resynthesis (recycling) of PIP2, leading to its relative depletion in neuronal membranes of the CNS.

 Lithium is well absorbed following oral administration. The drug distributes evenly to all tissues and body fluids. Lithium has a half life (15-30 h). The drug is administered in divided daily doses. Lithium is available in lithium carbonate, as capsules, standard tablets, slow release tablets, contains 300 mg lithium carbonate, dose 3 to 4 times daily.

 Sodium depletion will decrease renal excretion of lithium, thereby causing the drug to accumulate. Toxicity may result. Accordingly, it is important that sodium levels remain normal. Since diuretics promote sodium loss, these agents must be employed with caution. Sodium loss secondary to diarrhea can be sufficient to cause lithium accumulation.

 Lithium has a low therapeutic index ( mEq/L), greater than 1.5 mEq /L is toxic. Measurement of plasma lithium levels is an essential component of treatment. Lithium levels must be kept below 1.5 mEq/ L, levels greater than this can produce significant toxicity.

 Lithium is the drug of choice for patient with bipolar disorder. It control the manic episodes in these patients and it is used for long term prophylaxis against recurrent mania and depression in these patients.  The effect of lithium is start after 2 to 3 weeks, for this reason antipsychotic durg is initially administered with lithium, when lithium start to act the antipsychotic agent is then gradually withdrawn

 Adverse effects of lithium can be divided into 2 types:  Effects that occur at therapeutic drug levels.  Below 1.5 mEq/ L : nausea, vomiting, diarrhea, thirst, polyuria, muscle weakness, fine hand tremor.

 Adverse effects that occur when lithium levels are excessive:  Certain toxicities are closely correlated with the concentration of lithium in plasma:  Plasma levels exceed 1.5 mEq/ L: more serious toxicities appear.  mEq/L: Coarse hand tremor, confusion, sedation.  mEq/L: Ataxia, tinnitus, blurred vision and seizures.  Greater than 2.5 mEq/L symptoms may progress rapidly to generalized convulsions, oliguria and death.

 The most common cause of lithium accumulation is sodium depletion.  To keep lithium levels within the therapeutic rage, plasma drug levels should be monitored routinely.  Levels should be measured every 2 to 3 days at the beginning of treatment and every 1 to 3 months during maintenance therapy.

Polyuria occurs in 50% t0 70% 0f patients taking lithium chronically. Lithium promotes polyuria by antagonizing the effects of antidiuretic hormone. To maintain adequate hydration, patients should be instructed to drink 8 to 12 glasses of fluids daily.

Chronic administration of lithium has occasionally been associated with degenerative changes in the kidney. Kidney function should be assessed prior to treatment and once a year thereafter

Long term use of lithium can cause enlargement of the thyroid gland (goiter). Treatment with thyroid hormone or withdrawal of lithium will reverse thyroid hypertrophy. Measurement of thyroid hormones T3 and T4 and TSH should be obtained prior to treatment and annually thereafter.

Use of lithium during the first trimester of pregnancy is associated with an 11% incidence of birth defects( usually malformations of the heart). Accordingly lithium is contraindicated during the first trimester of pregnancy.

Lithium readily enters breast milk and can achieve concentrations that are potentially harmful to the nursing infant. Consequently breast feeding during lithium therapy should be discouraged.

Diuretics promote sodium loss and can thereby increase the risk of lithium toxicity by increasing lithium reabsorption from the renal tubules.

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