Antidepressants bipolar disorder

Antipsychotic medications are indicated in the treatment of acute and chronic psychotic disorders. These include schizophrenia, schizoaffective disorder, and manic states occurring as part of a bipolar disorder or schizoaffective disorder. The co-adminstration of antipsychotic medication with antidepressants has also been shown to increase the remission rate of severe depressive episodes that are accompanied by psychotic symptoms. Antipsychotic medications are frequently used in the management of agitation associated with delirium, dementia, and toxic effects of both prescribed medications (e.g. L-dopa used in Parkinson s disease) and illicit dtugs (e.g. cocaine, amphetamines, andPCP). They are also indicated in the management of tics that result from Gilles de la Tourette s syndrome, and widely used to control the motor and behavioural manifestations of Huntington s disease. 

The primary treatment for depressive episodes in bipolar disorder is mood-stabilizing agents, often combined with antidepressant drugs. 

Patients with bipolar disorder have a high risk of suicide. Factors that increase that risk are early age at disease onset, high number of depressive episodes, comorbid alcohol abuse, personal history of antidepressant-induced mania, and family history of suicidal behavior.15 In those with bipolar disorder, 1 of 5 suicide attempts are lethal, in contrast to 1 of 10 to 1 of 20 in the general population. 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

Mood stabilisers are used to regulate the cyclical change in mood characteristic of bipolar disorder, since they can attenuate both manic and depressive phases. Their main use is as a prophylactic for manic depression and unipolar mania. However, they can also be administered concomitantly with antidepressants for refractory (non-responsive) unipolar depression. 

Mundo E, Walker M, Cate T, Macciar-di F, Kennedy JL. The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder preliminary findings. Arch Gen Psychiatry 2001 58 539-544. 

Bipoiar Disorders. You must also distinguish the bipolar disorders from MDD. The distinction is particularly important in young adult patients given that nearly 10% of patients with an initial episode of major depression will go on to develop a bipolar illness. The devastating consequences of untreated mania coupled with the possibility that antidepressants may trigger manic episodes in susceptible individu-... 

In contrast to MDD, the bipolar disorders consist of episodes of depression and episodes of hypomania or mania. This poses a problem for treating the depressed phase of this illness, becanse, as noted earlier, antidepressants can trigger hypomania, mania, or mixed dysphoric mania and can increase the freqnency of manic episodes. Therefore, the hallmark of treating BPAD is the nse of mood stabilizers, with and withont snpplemental antidepressant therapy. Please refer to Table 3.16 for a comparison of the traditional mood stabilizers. 

Olanzapine (Zyprexa). The olanzapine molecule is structurally very similar to clozapine and therefore exerts very similar effects on brain receptors. The dose range of olanzapine for treating schizophrenia is from 5 to 30mg/day. Like clozapine, olanzapine appears to treat both positive and negative symptoms. It is also approved for the treatment of the manic phase of bipolar disorder. It has also been shown to augment the antidepressant effects of fluoxetine in refractory patients. 

Lithium chloride (Li" + Cl —> LICl) is used as an antidepressant, especially in the treatment of manic depression and bipolar disorders. 

Numerous open studies, and seven controlled studies, have shown that valproate is effective in the treatment of acute mania. It has also been claimed to have an antidepressant action. Recent studies have shown that valproate is effective in the long-term treatment of bipolar disorder. 

Screening patients for bipolar disorder Prior to initiating treatment with an antidepressant, adequately screen patients with depressive symptoms to determine if they are at risk for bipolar disorder. 

Screening patients for bipolar disorder A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Prior to initiating treatment with an antidepressant, adequately screen patients with depressive symptoms to determine if they are at risk for bipolar disorder. 

Psychosis or mania Antidepressants can precipitate manic episodes in bipolar disorder patients during the depressed phase of their illness and may activate latent psychosis in other susceptible individuals. The sustained-release formulation of bupropion is expected to pose similar risks. There were no reports of activation of psychosis or mania in clinical trials conducted in nondepressed smokers. 

D Sa C, Duman RS (2002) Antidepressants and neuroplasticity. Bipolar Disord 4 183-194 De Vry J (1995) 5-HTlA receptor agonists recent developments and controversial issues. Psychopharmacology (Berl) 121 1-26... 

The most common mood disorders are major depression (unipolar depression) and manic-depressive illness (bipolar disorder). Major depression is a common disorder that continues to result in considerable morbidity and mortality despite major advances in treatment. Approximately 1 in 10 Americans will be depressed during their lifetime. Of the 40,000 suicides occurring in the United States each year, 70% can be accounted for by depression. Antidepressants are now the mainstay of treatment for this potentially lethal disorder, with patients showing some response to treatment 65 to 80% of the time. 

In addition to its acute actions, Li+ can reduce the frequency of manic or depressive episodes in the bipolar patient and therefore is considered a mood-stabilizing agent. Accordingly, patients with bipolar disorder are often maintained on low stabilizing doses of Li+ indefinitely as a prophylaxis to future mood disturbances. Antidepressant medications are required in addition to Li+ for the treatment of breakthrough depression. 

Many of the children and adolescents seen for treatment of depression are experiencing their first depressive episode. Because the symptoms of unipolar and bipolar depression are similar, it is difficult to decide whether a patient needs only an antidepressant or concomitant use of mood stabilizers. As noted above, symptoms and signs such as psychosis, psychomotor retardation, or family history of bipolar disorder may warn the clinician about the risk of the child developing a manic episode. 

If relapse does occur, it should first be determined whether the patient was compliant with treatment. If the patient was not compliant, antidepressant medication should resume. If the patient was compliant and had been previously responding to the medication (without significant side effects), the existence of ongoing stressors (e.g., conflict, abuse) or comorbid medical or psychiatric disorders should be considered (anxiety disorder, ADHD, substance abuse, dysthymia, bipolar disorder, eating disorder). 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

These authors also examined which medications were prescribed to patients with specific diagnoses. The majority of antidepressants were prescribed for patients with major depression, dysthymia, or bipolar disorder. Antipsychotics were prescribed frequently for conduct/oppositional disorder, psychosis, and major depression or dysthymia. In the state hospital, the proportion of nonpsychotic patients who received antipsychotic treatment depended on patients age thus, the frequency of children who were not diagnosed with a psychotic disorder but who were treated with antipsychotic medication was greater among children 12 years and younger, in contrast to children ages 13 to 18 years. 

These authors also found that 65% (New York) and 67% (Ohio) of the sampled medicated patients who received an antipsychotic prescription were not diagnosed with a psychotic disorder. Similarly, 0% and 20% of the sampled medicated patients who received a stimulant medication were not diagnosed with ADHD, and 27% and 42% of the sampled medicated patients who received antidepressants were not diagnosed with major depression, dysthymia, bipolar disorder, or related conditions. In discussing the appropriateness of the medication treatments in the survey, the authors concluded that approximately 10% of the treatments in each sample were deemed inappropriate. 

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. 

Lambert 1984 McElroy et al. 1988b] suggested that valproate may be a much better antimanic than antidepressant agent. In a study of 78 consecutively recruited patients with rapid-cycling bipolar disorder treated with open-label valproate alone or in combination with other psychotropic agents, Calabrese and colleagues [Calabrese and Delucchi 1990 Calabrese et al. 1992] reported a 54% valproate response in acute mania, an 87% response in acute mixed states, and a 19% response in acute depression. However, they did observe a prophylactic antidepressant effect in patients subsequently. Additional controlled studies are needed to clarify valproate s antidepressant efficacy. 

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