There are two ways to describe the causes of agitation and aggression: by the underlying disease state (see Table 1), or the exact pathophysiology that causes the aggression. The DSM-IV-TR has several diagnostic categories describing the relationship between a medical condition or substance and the specific psychiatric symptoms or syndrome they cause. Examples of medical conditions that more commonly cause aggression and agitation symptoms include central nervous system disorders such as head trauma, stroke, tumor, and epilepsy; metabolic disorders such as fluid and electrolyte abnormalities, acid-base abnormalities, thiamine deficiency, hyper- and hypothyroidism, and hypoglycemia; infections such as sepsis, HIV, encephalitis, and urinary tract infections; and others such as systemic lupus erythematosus, postoperative states, especially in transplant or hip replacement procedures, terminal illnesses, and dialysis. Table 2 identifies medications and drugs that may be associated with inducing symptoms of agitation or aggression.

Four characteristics contribute to aggression and violence among people with serious mental illness: acute, poorly controlled mental illness, medication noncompliance, substance abuse, and previous violent behavior. Each is an independent risk factor, and the risk is heightened when factors are combined. People with and without mental illness who use drugs and alcohol have an increased risk for agitation and aggression.

There is no single unifying theory for the underlying pathophysiology of aggression. Brain lesions and changes in neurotransmitter function are two widely accepted theories. As the frontal lobes are responsible for higher order thinking, censoring, disciplining, planning and decision-making, damage to the frontal cortex produces a variety of disinhibited behaviors (patient becomes more agitated or aggressive than prior to receiving medication). Lesions or injury to the basal ganglia, limbic system, thalamus, hypo-thalamus, hippocampus and temporal lobes may also result in abnormal behavior. In a simplistic approach, agents that reduce dopaminergic or noradrenergic tone or increase serotonergic or GABAergic tone decrease aggression (such as any benzodiazepine or antipsychotic agent), no matter what the cause.

There is specific evidence demonstrating an inverse correlation between 5-HIAA, the major meta-bolite of serotonin, and aggressive behaviors.Other theories propose that the mechanism of agitated depression is increased serotonergic responsiveness and decreased GABAergic tone, whereas acute psychosis results from increased dopamine.The pathophysiology is generally more important when planning a long-term strategy to treat the underlying disease rather than when managing an acutely agitated patient who needs immediate attention.

Psychiatric Primary Care

Linda Denise Oakley, Claudette Potter
Mosby-Year Book, Inc, 11830 Westline Industrial Dr, St Louis, MO 63146 USA
1997/448 pp

Strengths

Assessment and DSM-IV diagnosis

Weakness

Specific pharmacologie treatment

Audience

Family physicians and allied mental health professionals

The authors of this ambitious book state, “We have developed a book for primary care practitioners that presents everything from basic mental concepts and terms to clinical examples of psychiatric primary care.”

The book is divided into five parts that deal with basic concepts of assessment and diagnosis; common mental disorders; psychosocial problems; special populations and problems, such as children; and practice notes covering mental health laws, threatening patients, and clinical vignettes.

Illnesses are conceptualized in the biopsychosocial model, and diagnoses are based on DSM-IV definitions. This book is very strong in assessing mental disorders, presenting epidemiologic data, risk factors, psychiatric terminology, and DSM-IV criteria. It is also strong in addressing the psychosocial context in which mental illnesses occur.

This book is too general in the area of management. For example, in treating depression, information on using specific medications and dosages is not provided. As well, while cognitive-behavioural therapy is mentioned, advice on how to use it in specific disorders is not given. This wide-angle perspective on management, especially pharmacologie treatment, probably arises from the nursing background and praètice of the authors.

It is important to note, given the book’s emphasis on DSM-IV diagnoses, that the DSM itself is continually evolving and that its diagnoses are based strictly on empirical clinical presentation. We would be wise to acknowledge the ambiguities of human nature and not thoughtlessly use formulae to reduce the complexities and richness of human expression into 5-digit codes.

This book excels in teaching attitude and background knowledge of psychiatric primary care. However, specific knowledge and skills are still required for proficient practice. The book describes certain important aspects of continuing education in psychiatric primary care for Canadian physicians.

The authors believe that psychiatry in general practice is a different specialty from psychiatry in hospitals. The authors suggest that a problem-oriented model is more appropriate to family practice. The authors also believe that psychoanalysis is a frame of reference that has outlived its usefulness and have introduced their textbooks with chapters on ethology, psychology, and social science, as well as an introduction to the excellent British literature on the epidemiology of psychiatric illness in general practice.

The bulk of the book focuses on practical management by the primary care team, the family life cycle and its turning points, mind and body relationships, and traditional psychiatric disorders.

This book is well written, comprehensive, and for the most part, the authors have met their objective of providing information about the problems in family practice. I do have several reservations about the book, which perhaps reflect my bias of being a psychiatrist trained in North America and not a British family physician.

There is too much background information in the relatively lengthy book and not enough focus on the common clinical presentations of anxiety, depression, and substance abuse. The reference material is largely from the literature in England, and while I found that fascinating, I wondered whether some of the references and contents were relevant to North American practice.

Finally, the sections on counseling and individual psychotherapy, family and couple therapy, group therapy, etc, are well written, but they seem to expect more of a family physician than training and experience would suggest is reasonable. This book (no. 15 in the Oxford General Practice series) is a good example of newer models and practices for psychological problems in general practice and provides an introduction to literature not available in North American books. There are, however, shorter and more practical paperbacks available in the marketplace.

Most initial published data on atypical antipsychotic drugs in the elderly are clinical trials in nondemented patients with schizophrenia or Parkinson’s disease. In the last two to three years, controlled trials evaluating risperidone (Risperdal) and olanzapine (Zyprexa) in patients with dementia have been published. There is now evidence that these two atypical antipsychotic drugs offer efficacy in this patient population with fewer adverse effect concerns than the typical antipsychotic drugs.

Risperidone (Risperdal). In 1999, Katz et al. published the first large multicenter, double-blind, placebo-controlled study of risperidone in treating psychosis and behavioral disturbances in an elderly demented population. Among the 625 patients, 73% had a diagnosis of Alzheimer’s disease; average age was 83 years; and their mean baseline Mini-Mental State Examination (MMSE) score was 6.6+6.3, indicative of the most severe stages of dementia. In this 12-week trial, patients received either placebo or risperidone 0.5 mg, 1 mg or 2 mg daily. At endpoint, significantly greater reductions in Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) total scores, as well as the psychosis and aggressiveness subscale scores were seen in patients receiving daily doses of 1 mg (p=0.005) and 2 mg (p=0.001) of risperidone compared to those receiving placebo. The 0.5 mg daily dose of risperidone was superior to placebo at week 12 in reducing BEHAVE-AD aggression scores (p=0.02). Improvement based upon total BEHAVE-AD scores for risperidone 1 mg or 2 mg was 56% in patients under 85 years old and 72% in older patients, while placebo response rate was 51% and 54%, respectively. While risperidone was clearly efficacious, the high placebo response rate indicates what Schneider (1999) described as “the waxing and waning and evanescence of disruptive behavior” in this patient population. The most common adverse effects from risperidone were motor symptoms, dose-related sedation and mild peripheral edema. Extrapyramidal symptoms did not differ significantly between placebo and risperidone 0.5 mg or 1 mg. Risperidone 2 mg daily produced significantly more parkinsonism and hypokinesia than placebo.

A 13-week study compared risperidone and haloperidol (flexible doses of 0.5 mg to 4 mg; 1 mg mean daily doses for both drugs) to placebo in 344 patients with dementia. At week 12, a reduction of 30% in the BEHAVE-AD total score was observed in 72%, 69% and 61% of patients receiving risperidone, haloperidol and placebo, respectively, and in 54%, 63% and 47% of patients by intention-to-treat analysis (no statistically significant difference). At endpoint, risperidone-treated patients did have significantly greater reductions in the aggressiveness scores compared to placebo. The most common adverse effects for both haloperidol and risperidone were sedation and falls, with haloperidol causing significantly more extrapyramidal effects.

Olanzapine (Zyprexa). In 2000, Street et al. published a large double-blind, randomized, placebo-controlled trial evaluating olanzapine in patients with Alzheimer’s disease. In this six-week trial, 206 patients were given placebo or a fixed olanzapine daily dose of either 5 mg, 10 mg or 15 mg. Mean baseline MMSE scores were 6.7+6.4, indicating severe dementia. Significantly greater improvements in agitation/aggression and delusions/hallucinations were observed in patients treated with olanza-pine 5 mg or 10 mg compared to placebo and olanzapine 15 mg. The most improvement was seen in patients treated with 5 mg. The total MMSE score did not change significantly over the course of the clinical trial, although there was a modest improvement in the 5 mg dose group and a modest decline in the 10 mg and 15 mg dose groups. Somnolence was the most common dose-related adverse effect, occurring in 25% to 36% of olanzapine-treated patients compared to 6% with placebo. Gait disturbance occurred in patients receiving 5 mg or 15 mg (20% and 17%, respectively), compared to 2% with placebo. There was no significant cognitive impairment, increase in extrapyramidal effects or central anticholinergic effects at any olanzapine dose compared to placebo. Vital signs and laboratory and electrocardiogram measures were unchanged in each dose group compared to placebo.

Discussion

The modest efficacy of conventional antipsychotic drugs in patients with dementia, coupled with their high potential for extrapyramidal effects, tardive dyskinesia, anticholinergic effects and worsening cognition has meant that many patients’ behavioral symptoms and psychosis have been inadequately treated. The atypical antipsychotic drugs, notably risperidone and olanzapine, now have evidence supporting their efficacy and lower potential for adverse effects. Daily doses of no more than 1 mg to 2 mg of risperidone or 5 mg to 10 mg olanzapine can provide significant therapeutic benefit without the risk of significant adverse effects compared to conventional antipsychotic drugs.

Effective pharmacologic and nonpharmacologic treatment of these symptoms is desirable and, in addition, might delay nursing home placement. Pharmacologic and nonpharmacologic interventions are indicated based upon consideration of the safety of both the patient and those around them. Conventional antipsychotic drugs have limited value for psychotic and behavioral symptoms, but recently the results of several large controlled trials of atypical antipsychotic drugs have become available.

Conventional Antipsychotics

The use of conventional antipsychotic drugs in patients with dementia has a long history of concerns regarding limited efficacy as well as adverse effects that often exceed any therapeutic benefits. In the 1980s, these concerns led to the nursing home provisions of the 1987 Omnibus Budget Reconciliation Act (OBRA 1987) mandating reductions of antipsychotic drugs in an effort to limit their use. OBRA 1987 identified specific indications for antipsychotic drugs that included psychotic symptoms and specific aggressive behaviors, and it also identified symptoms of impaired memory, uncooperative attitude, poor self-care and wandering as inappropriate indications for antipsychotic drug therapy. It was recognized that while low doses of conventional antipsychotic drugs (e.g., haloperidol [Haldol] 1 mg/day to 3 mg/day) could be effective for severe aggressive behaviors and psychotic symptoms, higher doses could in fact worsen cognition. Furthermore, extrapyramidal effects could limit improvements in quality of life achieved through improvement in behavioral symptoms.

In 1990, Schneider et al. published a meta-analysis of controlled clinical trials of conventional antipsychotic drugs published from 1954 to 1989. While the authors concluded that these drugs were effective, only 18% of patients received beneficial effects beyond those from placebo. A later meta-analysis evaluated published studies from 1962 to 1995 comparing conventional antipsychotic drugs to placebo in treating behavioral disorders of dementia. Their conclusion was similar in that no significant difference was found in efficacy between individual antipsychotic drugs, with a modest therapeutic benefit of 26% for antipsychotic drugs beyond that from placebo.

Thioridazine (Mellaril) and haloperidol have been the most commonly used drugs in this patient population. Thioridazine poses particular concerns regarding orthostasis, anticholinergic effects and sedation, while haloperidol carries a high risk of movement disorders and the need to use an anticholinergic drug to treat them. Daily doses of haloperidol above 2 mg or of thioridazine above 75 mg tend to be less effective and are associated with greater adverse effects.

Answer: You are raising a difficult and important question, and one which I can’t answer definitively without knowing more of your situation and symptoms. Feeling “stressed out” because of school and job pressures is fairly common, and – while unpleasant – not usually something requiring professional counseling or psychotherapy. Instead, trying to identify the specific stressors and reducing them as much as possible usually suffices.

For example, can you reduce your job hours at all? Can you find ways to organize your study time more efficiently?(There are many books out on this topic). If you can’t change your job or its hours, can you speak with your supervisor about the nature of the work itself? Are there aspects that could be changed to your liking? Do you have an academic or “peer” advisor who could provide guidance regarding your course load? Should you reconsider your major? etc.

Regarding “self-help” exercises, I assume you have in mind something like self-relaxation or stress reduction. Yes, you can certainly learn these. Herbert Benson’s The Relaxation Response is a good place to start. Various relaxation tapes can be purchased in most good book stores, and certainly can’t do you any harm.

On the other hand, you need to be more concerned if you are actually developing signs and symptoms of a “clinical” depression, or major depressive episode. Symptoms would include, e.g., depressed mood nearly every day for more than 2 weeks; markedly diminished interest or pleasure in most activities, nearly every day; significant weight gain or loss; insomnia or excessive sleep; severe fatigue; feelings of worthlessness or guilt, impaired concentration or inability to make decisions; or thoughts of ending your life, recurrent thoughts about death, etc. More than two or three of these features (or the presence of suicidal ideation alone) should first prompt a visit to your general or family doctor, or school clinic, for a physical exam and routine laboratory studies to rule out medical illness; e.g., low thyroid function, and other underlying physical problems.

If all this is “negative,” you should then consider getting a referral to a mental health professional (psychiatrist, psychologist, psychiatric social worker, or clinical nurse specialist) for psychotherapy and perhaps a trial of antidepressant medication. (Medication can be prescribed only by physicians or, under supervision in some states, clinical nurse specialists and physician assistants).

In the mean time, reading the book Feeling Good by David Burns may be helpful in learning ways of “thinking your way out” of depression. Good luck!

The integration of the drug therapies with other forms of psychiatric treatment will be the most important contribution of psychiatric research and therapy in our day. As usual, if some new therapeutic agent is introduced, we observe negation on the one hand and exaggeration on the other. We believe that pharmacotherapy is definite progress in psychiatric treatment and will benefit a number of patients. On the other hand, none of the known chemotherapeutic agents have been so effective that we can say whole psychiatric disorder entities will be wiped out, or as it has been stated, that hospitals will be closing and patients will not be admitted. These chemotherapeutic agents may somewhat reduce the admission rate to hospitals, but this has not been noticeable as yet. We have noted, however, that the discharge rate is higher in the mental hospitals. This may be due to the fact that the period of treatment of the patient can be shortened. There are some indications that patients who have been treated in a hospital and are now maintained on tranquilizing drugs outside of the hospital, do not relapse as often as patients who received other forms of treatment. We need more information on this very important point. If, after a comparatively short period of hospitalization, we could treat many of these patients, even if only on a symptomatic level and on an outpatient status, with the compounds we are using today for the treatment of psychoses such as schizophrenia, it would be a considerable achievement. We would like to call your attention to the fact that without any great fanfare and without even considering it spectacular, 80 per cent of epileptic patients are today controlled with the different chemical compounds now available, outside the hospital. This has been accomplished even though the etiology of epilepsy is unknown and the action of the chemical compounds on the epileptic disorder results in only symptomatic relief but does not affect the etiology.

The use of chemical compounds in psychiatry will be not only a symptomatic tool in controlling more effectively than heretofore some of the psychiatric disorders, but will lead inevitably to intensified research and a better understanding of the biochemical function of the nervous system and also a better understanding of the function of the nervous system in relation to emotional disorders.

A considerable number of patients become more amenable to psychotherapy while under the drug. Because the psychiatrist’s time is not absorbed by giving these patients reassurance, some of the adaptational difficulties and conflicts can be disclosed more rapidly and at times more incisively than otherwise. How psychotherapy should be applied to patients under the influence of the tranquilizing drugs is still under investigation. We are all groping in this field and no definite conclusions can be drawn. We do not know how far psychotherapy can be modified or applied over a much shorter period than has been customary in the past. Do the drugs support or replace certain psycho-therapeutic functions or not? It is also unclear how the psychotherapeutic techniques should be modified with patients under the influence of drugs. It is obvious that a patient who is not anxious, who is relaxed, and who is not constantly preoccupied with what is going on inside of himself is far better able to externalize interest and participate in group or in individual psychotherapy than otherwise. Even in optimum circumstances, psychotherapy with a psychotic individual is a very tedious, hard, and uncertain job. It is possible that with the help of the newer chemical compounds and perhaps even more with those still to be introduced, psychotherapy with these patients will become more effective and more economical of time.

Some psychiatrists have raised fears that many patients under the influence of these drugs will lose their anxiety. This is particularly true of some neurotic patients. In this event they would not have the motivation to undergo psychotherapy. It is possible that in some patients the drugs remove the discomfort and the patient will not seek any other psychiatric help. It is not yet clear if in those patients where the drugs are so successful that they are completely symptom free and functioning well, whether they really need further psychiatric treatment or not. This will have to be decided in each individual case.

Some psychiatrists also maintain that the extensive use of these drugs is deplorable because they deprive the patient of his incentive to undergo psychotherapeutic or analytic work which is the only treatment able to affect the patient’s emotional difficulties on a causal level. We would like to call attention to the fact that in present-day psychiatry there are only a few conditions where we are able to apply a causal treatment. Most of our treatments as used today, somatic or psychotherapeutic, are symptomatic. To be able to claim that psychotherapy does a causal etiological job in a psychotic individual would imply that we know the origin of these disorders. Based on present-day psychiatric knowledge, the etiology of quite a number of neurotic disorders is also obscure. Therefore, to assume that one treatment is symptomatic and another is causal is unwarranted.

Second, we believe that if a tranquilizing drug is prescribed, a proper indication for its use should be present. In other words, it should not become a reflex panacea, meaning that any and every kind of nervous and emotional complaint should be treated by giving one or another of the tranquilizing drugs. It would be deplorable if the emotional complaints of the patient were not assessed and properly evaluated, and if all forms and kinds of emotional disorders regardless of how they occur, in what configuration they manifest themselves, and what causes are behind them, would be treated by the administration of a tranquilizing drug.

Another difficulty which we frequently encounter is that the patient is not kept under close enough medical surveillance as to what mental and physical symptoms he may develop under the influence of these drugs. The first few weeks of treatment with these drugs are a crucial time and frequent observation of the patient is essential. We have seen patients develop depressions who were told to take the medication and to return in two or three weeks, with the assumption that the drug would either help or not help, but that it could not produce undesirable effects. Many physicians are aware of some of the physical complications which can be produced by these drugs, but are far less aware of the mental alterations which can be observed. Fortunately, in the majority of the patients there is an amelioration, but in some there is an aggravation, of the existing symptomatology and sometimes even new symptoms occur.

A patient who is using the drug on a maintenance dosage level does not have to be seen as frequently as a patient still under full treatment. However, even patients who are on a maintenance dose should be seen every few weeks to determine whether or not the drug still controls the symptoms, whether the amount given can be reduced, or even if the drug can be withdrawn. It is also important to decide whether the patient will or will not require psychiatric help in addition to the drug treatment.

There is considerable controversy in the literature as to how long the treatment of a patient should be continued when he is responding well to a drug. Should such a patient be treated for a few months and then cut off or should the patient be given the drug indefinitely? In a certain number of patients it is possible to stop the drug after a few weeks or months and then find that the patient is able to get along without it. We regret to say that in a large number of psychotic patients and also in a considerable number of neurotic patients responding to the drug, it will have to be continued for a long time — if not indefinitely. If the drug is withdrawn the clinical symptoms of the patient recur, sometimes gradually and slowly, and at other times quite suddenly. It has not yet been determined how long a patient should be maintained on a drug and more information than we have today must be obtained on this important point.

In addition to discussing uses of tranquilizing drugs in a general way, we have also been asked to discuss their abuses. It is obvious that with any new treatment approach, and especially if it develops fairly rapidly, certain abuses also develop. These abuses are even more understandable if we consider that the etiology of many of the disorders is unknown. The use of these compounds therefore cannot be applied as specifically and clearly as in disorders with a known origin. However, this does not mean that in some instances the tranquilizing drugs are not used indiscriminately.

The American Psychiatric Association recently issued a statement concerning the use of these drugs by the public for the relief of everyday tensions. It outlined the contributions made by these drugs to psychiatric practice. At the same time it pointed out that these drugs are used by the public for the relief of common anxiety, emotional upsets, nervousness, and the routine tensions of everyday living. A market research firm has stated that thirty-five million prescriptions for such drugs were filled in 1956 and that three out of ten prescriptions written by physicians in 1955 were for tranquilizers. We do not want to enlarge here on the public health aspects of this observation. You will recognize that in this situation we are not dealing with abuses alone, but we are faced with a tremendous demand to regulate nervous tension and anxiety by medication. An unsuspected large segment of the population is obviously seeking a safe tension-reducing agent. We believe that in addition to the psychiatric and medical measures which must be taken to delineate the indications for these drugs for different emotional disorders, it will be necessary to study in detail the reasons why such a great demand exists in the population for such drugs that have this tension-reducing property and why such a large segment of the population feels they are in need of such support and relief.