The motor symptoms of Parkinson's disease (PD) are caused primarily by degeneration of dopaminergic neurons in the substantia nigra. The nonmotor symptoms of the disease are thought to be caused by degeneration of other neurotransmitter systems. No disease-modifying drugs are available for treatment of PD.

The FDA has approved lumateperone (Caplyta — Intracellular Therapies), an oral second-generation antipsychotic, for once-daily treatment of schizophrenia in adults. It is the 13th second-generation antipsychotic drug to be approved by the FDA for this indication.

The FDA has approved deutetrabenazine (Austedo – Teva), a vesicular monoamine transporter 2 (VMAT2) inhibitor, for treatment of chorea associated with Huntington's disease and, more recently, for treatment of tardive dyskinesia in adults. It is the second VMAT2 inhibitor to be approved for each of these indications; tetrabenazine (Xenazine, and generics) was approved earlier for Huntington's chorea and valbenazine (Ingrezza) was recently approved for treatment of adults with tardive dyskinesia.

The motor symptoms of Parkinson's disease (PD) are caused primarily by degeneration of dopaminergic neurons in the substantia nigra. The nonmotor symptoms of the disease are thought to be caused by degeneration of other neurotransmitter systems.

The FDA has approved valbenazine (Ingrezza – Neurocrine Biosciences), a vesicular monoamine transporter 2 (VMAT2) inhibitor, for treatment of tardive dyskinesia in adults. It is the first drug to be approved in the US for this indication; two other VMAT2 inhibitors, tetrabenazine (Xenazine, and generics) and deutetrabenazine (Austedo), were approved earlier for treatment of chorea associated with Huntington's disease.

The FDA has approved the atypical antipsychotic pimavanserin (Nuplazid – Acadia) for treatment of hallucinations and delusions associated with Parkinson's disease. It is the first drug to be approved in the US for this indication.

The FDA has approved cariprazine (Vraylar – Actavis), an oral, once-daily, second-generation antipsychotic, for treatment of schizophrenia and for acute treatment of manic or mixed episodes associated with bipolar I disorder.

The FDA has approved two new long-acting injectable formulations of second-generation antipsychotics for treatment of schizophrenia: aripiprazole lauroxil (Aristada – Alkermes), which is given once every 4-6 weeks, and paliperidone palmitate (Invega Trinza – Janssen), which is given once every 3 months. Once-monthly injectable formulations of aripiprazole (Abilify Maintena) and paliperidone palmitate (Invega Sustenna) were approved earlier.

The FDA has approved the oral, once-daily, second-generation antipsychotic brexpiprazole (Rexulti – Otsuka/Lundbeck) for treatment of schizophrenia and as an adjunct to antidepressants for treatment of major depressive disorder (MDD). Aripiprazole (Abilify), a structurally similar second-generation antipsychotic also comarketed by Otsuka (with BMS), recently became available generically.

The motor symptoms of Parkinson's disease (PD) are caused primarily by progressive degeneration of dopaminergic neurons in the substantia nigra. The non-motor symptoms of the disease are thought to be caused by degeneration of other neurotransmitter systems.

Alzheimer's disease (AD) is the most common cause of dementia, but cognitive loss is also associated with other neurological conditions such as Parkinson's disease, dementia with Lewy bodies, and vascular dementia. Mild cognitive impairment (MCI) is generally defined as cognitive decline greater than expected for an individual's age and educational level, but not interfering with activities of daily living; it may be a transitional state between the cognitive changes of normal aging and dementia.

Drugs are not the only treatment for psychiatric illness. Psychotherapy remains an important component in the management of these disorders, and cognitive behavioral therapy (CBT) can be used for many of them as well. Electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective or cannot be used.

The FDA has approved lurasidone (Latuda - Sunovion), a new second-generation antipsychotic, for oral treatment of schizophrenia in adults.

Glycopyrrolate (Robinul, and others), a synthetic muscarinic receptor antagonist, has been used off-label for many years for treatment of excessive drooling in patients with Parkinson’s disease, in patients taking clozapine for schizophrenia, and in developmentally disabled children.1-3 It has now been approved by the FDA as Cuvposa (Shionogi) for use specifically in children 3-16 years old with severe chronic drooling due to a neurologic condition, such as cerebral palsy. It is being marketed as an oral solution, which will permit more precise weight-based dosing than was possible with the oral tablets used in the past. As with other anticholinergic drugs, dry mouth, constipation, flushing and nasal congestion can occur. Since glycopyrrolate decreases secretion not only of saliva, but also of sweat, overheating due to high ambient temperatures or excessive exercise could be dangerous for patients who take it.

1. ME Arbouw et al. Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology 2010; 74:1203.

2. CS Liang et al. Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study. Schizophren Res 2010; 119:138.

3. RJ Mier et al. Treatment of sialorrhea with glycopyrrolate: a double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000; 154:1214.

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Parkinson’s disease (PD) is caused primarily by progressive degeneration of dopamine-containing neurons in the substantia nigra. Dopamine itself cannot be used to treat PD because it does not cross the blood-brain barrier.

The antipsychotic drugs listed in Table 1 on the next page are more effective for treating the “positive symptoms” of schizophrenia (hallucinations and delusions) than the “negative symptoms” (apathy, social withdrawal, and blunted affect). Some symptoms of schizophrenia and acute psychoses may improve rapidly after treatment with antipsychotic drugs, but chronic schizophrenia improves slowly over many weeks and some patients may continue to improve for months. Most patients with chronic schizophrenia require prolonged maintenance therapy, but the risk of tardive dyskinesia and adverse metabolic effects must be kept in mind.

Drugs are not the only treatment for mood disorders. Psychotherapy remains an important component in the management of these disorders, and electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective, poorly tolerated or cannot be used. Some drugs are recommended here for indications that have not been approved by the FDA.

The FDA has approved the marketing of iloperidone (Fanapt – Vanda), a second-generation antipsychotic, for treatment of schizophrenia. Iloperidone is chemically related to risperidone (Risperdal, and others).

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment could also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

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Peptic ulcers caused by treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) are mainly gastric ulcers. The greater the number of office visits and the longer the counseling time, the higher the smoking cessation rates have been.

ParkinsonÆs disease (PD) is caused primarily by progressive degeneration of dopamine-containing neurons in the substantia nigra. Dopamine itself cannot be used to treat PD because it does not cross the bloodbrain barrier.

Drugs are not the only treatment for psychiatric illness. Psychotherapy remains an important component in the management of these disorders, and cognitive behavioral therapy (CBT) is used for many of them as well. Electroconvulsive therapy (ECT) has a long history of efficacy and safety when drugs are ineffective or cannot be used.

Aripiprazole (Abilify - Bristol-Myers Squibb/Otsuka), a second-generation (atypical) antipsychotic drug, was approved by the FDA in 2002 for treatment of schizophrenia and more recently for bipolar disorder as well. It has been promoted as causing fewer adverse effects than other antipsychotics, without sacrificing efficacy.

The FDA has reported that 5106 elderly patients with dementia treated with atypical (second generation) antipsychotics in 17 randomized controlled trials had a higher mortality rate (4.5% vs. 2.6%) than those receiving placebo. Most of the deaths were due to cardiovascular and infectious causes (such as pneumonia). The drugs used in the trials were aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal). As the increase in mortality was considered a class effect, the FDA advisory also included ziprasidone (Geodon), clozapine (Clozaril) and the olanzapine/fluoxetine combination (Symbyax). The manufacturers of all of these drugs will be required to add a "black box" warning to their labeling.

Parkinson's disease is caused by progressive degeneration of dopamine-containing neurons in the substantia nigra. Dopamine itself cannot be used to treat Parkinson's disease because it does not cross the blood-brain barrier.

A recent supplement to the Journal of Clinical Psychiatry, titled "The Expert Consensus Guideline Series: Optimizing Pharmacologic Treatment of Psychotic Disorders," concluded that most experts endorsed use of second-generation (atypical) antipsychotics rather than first-generation drugs, with risperidone (Risperdal - Janssen) the top choice for first episodes, multiple episodes or switches from another drug (JM Kane et al, J Clin Psychiatry 2003; 64 suppl 12:5). The supplement was sponsored by Janssen.

The number of drugs marketed for psychiatric indications has increased sharply in recent years. The recommendations in this article are based on the results of controlled trials and on the experience and opinions of Medical Letter consultants. Interactions with other drugs can be found in The Medical Letter Handbook of Adverse Drug Interactions, 2003.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Aripiprazole (Abilify - Bristol-Myers Squibb/Otsuka), a quinolinone derivative, has been approved by the FDA for treatment of schizophrenia.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment may also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

Ziprasidone (Geodon - Pfizer), a benzisothiazolyl piperazine, has been approved by the FDA for oral treatment of schizophrenia. An intramuscular formulation will probably be available in the near future.

Quetiapine (Seroquel - Zeneca), a dibenzothiazepine derivative, has been approved by the FDA for treatment of schizophrenia and other psychotic disorders. It is a new addition to the 'atypical' antipsychotics, which include olanzapine (Zyprexa - Medical Letter, 39:5, 1997), risperidone (Risperdal) and clozapine (Clozaril). Atypical antipsychotic drugs generally are less likely to cause extrapyramidal symptoms than older drugs such as haloperidol (Haldol, and others) or the phenothiazines.

The number of new drugs marketed for psychiatric indications has increased sharply in recent years. The recommendations in this article are based on the results of controlled trials and on the experience and opinions of Medical Letter consultants. Interactions with other drugs can be found in The Medical Letter Handbook of Adverse Drug Interactions, 1997.

Olanzapine (Zyprexa - Lilly), a thienobenzodiazepine that structurally resembles and binds to many of the same receptors as clozapine (Clozaril), is now available in the USA for treatment of schizophrenia and other psychotic disorders.

Fluvoxamine (Luvox - Solvay), a selective serotonin reuptake inhibitor (SSRI), has been approved for treatment of obsessive-compulsive disorder (OCD) by the US Food and Drug Administration. Fluoxetine (Prozac), another SSRI antidepressant, and clomipramine (Anafranil), a tricyclic antidepressant that also inhibits serotonin reuptake, are the only other drugs available for this indication in the USA. Antidepressants that do not inhibit serotonin reuptake have not been effective for treatment of this condition.

Risperidone (Risperdal - Janssen), a benzisoxazole derivative, is now available in the USA for treatment of schizophrenia and other psychotic disorders.

Approaches to treatment of Parkinson's disease have changed in recent years. Previously, the only goal was to treat symptoms with levodopa or other drugs. A new approach is to try to slow progression of the disease. (This issue is superseded by 1999 Drugs of Choice.)

Clozapine (Clozaril - Sandoz), an antipsychotic drug, was first marketed in the USA three years ago (Medical Letter, 32:3, 1990). Because of its hematological toxicity, the US Food and Drug Administration approved the drug only for patients with schizophrenia who cannot tolerate or do not respond to standard antipsychotic drugs.