Mood stabilizers antipsychotic drugs

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

The first mood stabilizer was lithium (its antimanic action being discovered in 1948) more recently the anticonvulsant drugs carbamazepine and valproate have been found to be effective in acute mania. Unfortunately these mood stabilizers are only successful in controlling mania to a limited extent and few patients are well enough to leave hospital at the end of 3 weeks of treatment using these drugs as monotherapy. It is increasingly common for combination treatment to be advocated, in which an antipsychotic dmg is combined with lithium or an anticonvulsant. 

The primary treatment modality for manic episodes is mood-stabilizing agents, often combined with antipsychotic drugs. 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

It is common for lithium to be combined with other mood-stabilizing drugs or antipsychotic drugs, if necessary, in order to achieve more complete remission of symptoms. Studies indicate that monotherapy is often insufficient to reach this goal.17... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

Prescribing of psychotropic drugs, such as antipsychotics, antidepressants, anxiolytics and mood stabilizers, is common in psychiatric inpatients for acute and maintenance treatment of psychiatric illness. 

High-potency benzodiazepines (e.g., clonazepam and lorazepam) are common alternatives to or in combination with antipsychotics for acute mania, agitation, anxiety, panic, and insomnia or in those who cannot take mood stabilizers. Lorazepam IM may be used for acute agitation. A relative contraindication for long-term benzodiazepines is a history of drug or alcohol abuse or dependency. 

Lithium remains the treatment of choice for bipolar patients who experience classic euphoric episodes of mania. Current evidence suggests that those with mixed episodes or rapid cycling episodes respond preferably to anticonvulsants or atypical antipsychotic drugs. In addition to its use as a mood stabilizer, lithium is effective in converting unipolar antidepressant nonresponders to responders. Finally, lithium may also be an effective treatment for patients with clnster headaches. 

Lithium, several (but not all) anticonvulsants, and most of the atypical antipsychotic medications are approved by the U.S. Food and Drug Administration (FDA) for the treatment of one of more phases of bipolar disorder. These medications are referred to as mood stabilizers, and they are the foundation of treatment for bipolar disorders. However, the skillful treatment of bipolar disorder requires not only the knowledge of how to prescribe one or more of these medications but also the understanding that some medications are preferred for one phase of the illness but not the other or for long-term use but not necessarily acute use. In this chapter, we first review the clinical use of lithium and the anticonvulsants that are definite or probable mood stabilizers. The general properties of atypical anti-psychotics are reviewed in Chapter 4. In this chapter, we expand on the use of these compounds for the treatment of bipolar disorder. Discussion of the treatment of each phase of bipolar disorder concludes the chapter. 

Psychotropic effect is the main effect, with the desired action Psvchopharmaceuticals Antipsychotics Antidepressants Mood stabilizers Anxiolytics, hypnotics Psychostimulants Nootropics, antidementia drugs Social drugs , drugs Alcohol Nicotine Cocaine, heroin, etc. 

The following sections of this chapter concentrate on psychopharmaceuticals in the sense of Table 1.1, Le. antipsychotics. antidepressants, mood stabilizers, anxiolytics and psychostimulants attention also will be paid to hypnotics and antidementia drugs. 

Problems of optimal dosage and duration of drug treatment for mental disorders have also been addressed in numerous controlled studies and are presented separately below for antipsychotics, antidepressants, mood stabilizers, anxiolytics and psychostimulants. This division again makes sense because the disorders treated and the therapeutic approaches used differ in significant aspects and the empirical studies carried out in the individual indications show major qualitative and quantitative differences. 

Generally, one drug should be started at a time so that its results can be evaluated. Occasionally, emergency or practical considerations dictate starting more than one drug simultaneously, but later one can undergo a therapeutic discontinuation (e.g., antipsychotic plus mood stabilizer in a severe manic episode). While the addition of several medications does occur, we emphasize that the clinician should evaluate and document the patient s response to each newly added medication. 

Unfortunately, for a number of methodological and clinical reasons, the success achieved with this strategy for other classes of drugs (e.g., certain mood stabilizers) has not been achieved with the monitoring of antipsychotic steady state plasma concentrations. Difficulties in study design have contributed to this uncertainty, including ... 

Analogous to the recent progress in antidepressant and antipsychotic drug therapy development the pharmacotherapy of bipolar disorder is also experiencing major advances. Data on the efficacy of mood stabilizers for bipolar disorder focus on the following ... 

Other mood stabilizers are arising from the group of drugs that were first developed as anticonvulsants and have also found an important place in the treatment of bipolar disorder. Several anticonvulsants are especially useful for the manic, mixed, and rapid cycling types of bipolar patients and perhaps for the depressive phase of this illness as well. Mood stabilizers will be discussed in detail in Chapter 7. An-tipsychotics, especially the newer atypical antipsychotics, are also useful in the treatment of bipolar disorders. 

FIGURE 7—35. Combination treatments for bipolar disorder (bipolar combos). Combination drug treatment is the rule rather than the exception for patients with bipolar disorder. It is best to attempt monotherapy, however, with first-line lithium or valproic acid, with second-line atypical antipsychotics, or with third-line anticonvulsant mood stabilizers. A very common situation in acute treatment of the manic phase of bipolar disorder is to treat with both a mood stabilizer and an atypical antipsychotic (atypical combo). Agitated patients may require intermittent doses of sedating benzodiazepines (benzo assault weapon), whereas patients out of control may require intermittent doses of tranquil-izing neuroleptics (neuroleptic nuclear weapon). For maintenance treatment, patients often require combinations of two mood stabilizers (mood stabilizer combo) or a mood stabilizer with an atypical antipsychotic (atypical combo). For patients who have depressive episodes despite mood stabilizer or atypical combos, antidepressants may be required (antidepressant combo). However, antidepressants may also decompensate patients into overt mania, rapid cycling states, or mixed states of mania and depression. Thus, antidepressant combos are used cautiously. 

This chapter will explore the various drug treatments for psychotic disorders, with special emphasis on schizophrenia. Such treatments include not only conventional antipsychotic drugs but also the newer atypical antipsychotic drugs, which are rapidly replacing the older conventional agents. We will also take a look into the future at the drugs under development for psychosis, especially schizophrenia. Mood stabilizers for bipolar disorders were covered in Chapter 7. 

Drugs can not only be substrates for a cytochrome P450 enzyme or an inhibitor of a P450 enzyme, they can also be inducers of a cytochrome P450 enzyme and thereby increase the activity of that enzyme. This was discussed in Chapter 6 for CYP450 3A4, and the induction of 3A4 activity by the anticonvulsant and mood stabilizer carbamazepine was given as an example (Fig. 6—19). Since mood stabilizers may be frequently mixed with atypical antipsychotics, it is possible that carbamazepine may be added to the regimen of a patient previously stabilized on clozapine, quetiapine, ziprasidone, or sertindole. If so, the doses of these atypical antipsychotics may need to be increased over time to compensate for the induction of 3A4 by carbamazepine. 

Profound mood-stabilizing effects of the atypical antipsychotic drugs were observed once their antipsychotic effects were documented. These effects on mood appear to be quite independent of their effects on positive symptoms of psychosis. The most dramatic story may be how impressive the atypical antipsychotics are turning out to be for the treatment of bipolar disorder (Fig. 11 — 53). Although the best documented effect of these drugs is to reduce psychotic symptoms in the acute manic phase of bipolar disorder, it is clear that these agents also stabilize mood and can help in some of the most difficult cases, such as those marked by rapid cycling and mixed simultaneous manic-depressed states that are often nonresponsive to mood... 

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