Manic-depressive disorder drugs used

Dr. J. F. J. Cade, an Australian psychiatrist, first reported on the beneficial use of a lithium compound for a psychiatric disorder, namely, manic behavior in 1949. The early human trials were undertaken after initial experiments on rats, which became quite lethargic after treatment with lithium urate. Fairly large doses were required for treating manic behavior and its use for this disorder has been displaced by organic drugs that carry less risk. His report, however, led to its current nse as a treatment for bipolar affective disorder (also known as manic-depressive disorder). Its use in the United States was curtailed for a decade and a half by the US. Food and Dmg Administration (FDA), which based its decision on incidental poisonings due to overuse of a lithium-based table salt substitute, despite a safe record of controlled psychiatric apphcations in Europe. It has been estimated that by 1985... 

Fluanisone is a neuroleptic with sedative properties and relatively poorly expressed antipsychotic action. It is used as an independent or adjuvant drug for psychomotor excitement in severe and chronic schizophrenia and for manic-depressive disorder. Synonyms of this drug are sedalande, methorin, and others. 

The depressive phase of manic-depressive disorder often requires concurrent use of an antidepressant drug (see Chapter 30). Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings, although most patients do not show this effect. Selective serotonin reuptake inhibitors are less likely to induce mania but may have limited efficacy. Bupropion has shown some promise but—like tricyclic antidepressants—may induce mania at higher doses. As shown in recent controlled trials, the anticonvulsant lamotrigine is effective for many patients with bipolar depression. For some patients, however, one of the older monoamine oxidase inhibitors may be the antidepressant of choice. Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. 

What had once been a relatively rare disorder, for which there was considered to be only one very specific treatment is now regarded as a widespread problem with an array of new drug treatments. In addition, the concept of the mood stabiliser allows drugs for manic depression to be used in many other situations in which there appears to be some instability of mood. Since almost by definition acute psychiatric disorders involve extreme emotional responses, almost any psychiatric patient can qualify for treatment with a mood stabiliser. My clinical experience suggests the use of these drugs among psychiatric patients has expanded considerably. 

There is no established way whereby allegedly unsafe drugs can find their nonprimary indications, but safe ones find many indications. This is an important part of the business of the drug industry. To nonscientists it may be surprising that antiepileptics have a variety of uses especially in pain treatment and, less often, as mood stabilizers for people with bipolar—or manic-depressive—disorder. 

A number of drugs inhibit the antidiuretic actions of vasopressin. Lithium is of particular importance because of its use in the treatment of manic-depressive disorders. Lithium-induced polyuria is usually reversible. Acutely, lithium appears to reduce V -receptor-mediated stimulation of adeny-lyl cyclase. Also, hthium increases plasma levels of parathyroid hormone, a partial antagonist to vasopressin. In most patients, the antibiotic demeclocycline attenuates the antidiuretic effects of vasopressin, probably owing to decreased accumulation and action of cyclic AMP. 

LITHIUM OTHER DRUGS USED IN BIPOLAR (MANIC-DEPRESSIVE) DISORDER... 

Depression is a common condition with both psychologic and physical manifestations. The three major types of depression are (1) reactive depression, a response to external events (2) bipolar affective (manic-depressive) disorder, described in Chapter 29 and (3) major depressive disorder, or endogenous depression, a depression of mood without any obvious medical or situational causes. The drugs used in major depressive disorder are the subject of this chapter. 

Haloperidol was introduced for the treatment of psychoses in Europe in 1958 and in the United States in 1967 (Fig. 22.7). it is an effective aiternative to more famiiiar antipsychotic phenothiazine drugs and also is used for the manic phase of bipolar (manic-depressive) disorder. Haloperidol decanoate has been introduced as depot maintenance therapy. When injected every 4 to 6 weeks, the drug appears to be as effective as daily orally administered haloperidol. Other currently available (mostly in Europe) butyrophenones include the very potent spiperone (spiroperidol) as well as trifluperidol and droperidol. Droperidol, a short-acting, sedating butyrophenone, is used in anesthesia for its sedating and antiemetic effects and, sometimes, in psychiatric emergencies as a sedative-neuroleptic. Droperidol often is administered in combination with the potent narcotic analgesic fentanyl for preanesthetic sedation and anesthesia. 

Lithium is the simplest therapeutic agent for the treatment of depression and has been used for over 100 years—lithium carbonate and citrate were described in the British Pharmacopoeia of 1885. Lithium therapy went through periods when it was in common use, and periods when it was discouraged. Finally, in 1949, J.J.F. Cade reported that lithium carbonate could reverse the symptoms of patients with bipolar disorder (manic-depression), a chronic disorder that affects between 1% and 2% of the population. The disease is characterized by episodic periods of elevated or depressed mood, severely reduces the patients quality of life and dramatically increases their likelihood of committing suicide. Today, it is the standard treatment, often combined with other drugs, for bipolar disorder and is prescribed in over 50% of bipolar disorder patients. It has clearly been shown to reduce the risk of suicide in mood disorder patients, and its socioeconomic impact is considerable—it is estimated to have saved around 9 billion in the USA alone in 1881. 

The use of lithium in medicine has been the subject of recent reviews by Birch,81 Birch and Sadler29 and references therein, and Tosteson.82 Historically, the use of lithium in medicine began with the treatment of gout and rheumatics in 1859. For the following 90 years, lithium was proposed for a variety of disorders and then discarded for example, lithium bromide was considered to be an effective sedative. In 1949 lithium was introduced into psychiatric practice and lithium carbonate, LijCOj, became the first of the modern psychotropic drugs. In a review of double-blind trials Schou and Thomsen (1975) support the prophylactic use of this drug in bipolar (manic-depressive) illness. 

Valproic acid (Depakene, Depakote, other trade names) is classified as a carboxylic acid, and is used primarily to treat absence seizures or as a secondary agent in generalized tonic-clonic forms of epilepsy. This drug is also used to treat bipolar disorder (manic-depression), especially during the acute manic phase (see Chapter 7). 

Interactions with other drugs have been less closely studied, but anecdotal reports suggest that lithium, a drug used to stabilize mood in people with manic depression or bipolar disorder, increases the response to LSD. 

Lithium is an alkaline earth element that is used medicinally in the form of salts such as lithium chloride and lithium carbonate. Its main use is in the prevention or attenuation of recurrent episodes of mania and depression in individuals with bipolar mood disorder (manic depression). Lithium also has clearly established antima-nic activity, although its relatively slow onset of action often necessitates the use of ancillary drugs, such as antipsychotic drugs and/or benzodiazepines, at the start of therapy. If lithium alone is ineffective for recurrent bipolar mood disorder, combining it or replacing it with car-bamazepine or valproate may be of value reports with lamotrigine and olanzapine are also encouraging. 

Lithium is the major drug used to treat the mood disorders of mania and manic-depressive illness. Lithium is the only psychotherapeutic drug that is an effective prophylaxis against disease recurrence. 

ANTIMANIC AGENTS are used mainly to treat manic-depressive illness (bipolar disorder), which is characterized by periods of mood normality punctuated by episodes of mania and bouts of depression. The manic phase most often requires acute treatment, and initially ANTIPSYCHOTIC AGENTS, e.g. phenothiazines, will usually be given. Thereafter, a very different psychoactive drug, lithium, may gradually be substituted in most patients, and this can prevent or reduce... 

The psychotic disorders include schizophrenia, the manic phase of bipolar (manic-depressive) illness, acute idiopathic psychotic illnesses, and other conditions marked by severe agitation. All exhibit major disturbances in reasoning, often with delusions and hallucinations. Several classes of drugs are effective for symptomatic treatment. Antipsychotic agents also are useful alternatives to electroconvulsive therapy (ECT) in severe depression with psychotic features, and sometimes are used in the management of patients with psychotic disorders associated with delirium or dementia or induced by other agents (e.g., stimulants or L-DOPA). 

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