BIOLOGICAL TREATMENTS – FROM SURGERY TO DRUGS
Until the late eighteenth century, people suffering from a psychological disorder were thought to be possessed by demons or evil spirits. Treatment was designed to alter the body in order to let out the spirits or make it an inhospitable habitat for them. Among the earliest biological treatments was ‘trepanning’, or removing part of the skull bone to allow evil spirits out of the body – a practice that endured until the twentieth century. Numerous other equally unpleasant biological assaults on the afflicted included bloodletting, beatings, purgatives and immersion in water to the point of near drowning. With the demise of witchcraft, people with psychological disorders came to be seen as ill, and the traditional methods of medicine began to be applied to them. But until the advent of the twentieth century, medical treatments were little different from the methods used to drive out evil spirits and were equally unsuccessful.
PSYCHOSURGERY AND ECT
Psychosurgery
Psychosurgery involves severing or otherwise disabling areas of the brain to treat a psychological disorder in the absence of any clear organic cause. Its use was triggered by research on chimpanzees that demonstrated the role of the temporal and frontal cortex in the control of emotional behaviour and aggression. Antônio Egas Moniz, of the University of Lisbon Medical School, developed a procedure in which the nerve fibres connecting the frontal lobe with other parts of the brain were cut. The prefrontal lobotomy became particularly popular in the USA, where a simple technique (that came to be known as ‘ice pick’ surgery) was administered during an outpatient visit (see figure 16.1). As a result, over 50,000 lobotomies had been performed in the United States by the mid 1950s (Cosgrove, 2000).The lobotomy has been replaced by the cingulotomy,in which neurosurgeons make lesions in the cingulate gyrus,a section of the brain connecting the prefrontal cortex to the limbic system (brain structures involved in autonomic body functions and some emotion and behaviour . Baer and colleagues (1995) found that this procedure,which had few side effects, successfully decreased anxiety andobsessive behaviour. But recent studies demonstrate that cingulotomy produces substantial benefits in only about a third of patients (Cosgrove, 2000).Although the number of psychosurgeries performed worldwide today isn’t known, it is estimated that fewer than 25 occur annually in Britain and the United States, about five a year in Sweden and one or two in Australia. Only people with very severe, disabling psychological disorders that resist other forms of treatment are even considered for psychosurgery today.Electroconvulsive therapy Another controversial treatment, and one that is still used fairly widely, is electroconvulsive therapy (ECT). In England 11,340 patients received ECT in 1999 (Department of Health, 1999).
Two electrodes are placed on the scalp and a moderately intense electric current is passed
between them for about half a second. This produces a 30- to 60- second seizure, similar to those experienced by epileptics. Today, short-acting anaesthetics and muscle relaxants are given prior to ECT, reducing the seizure to a few visible twitches. The usual course involves between four and twelve treatments over a oneor two-week period. ECT was initiated in the 1930s to treat schizophrenia, in the mistaken belief that epilepsy and schizophrenia are incompatible. It proved to be an ineffective treatment for schizophrenia but isnow widely believed to be effective in treating severe depression (Royal College of Psychiatrists, 1995). It is often used to treat depressed people who have not responded to antidepressant medication, can’t take medication because of the risk of suicide or other medical considerations, or risk death through refusal to eat.
Despite claims of ‘marked improvement . . . in 80% to 90% of patients’ (Silver, Yudovsky & Hurowitz, 1994, p. 983), the case for ECT is far from clear-cut. The consensus from clinical practice is that it can have beneficial effects, but research shows that the effects are relatively short-term. For example, compared to a sham treatment (i.e. the same procedure but with no current passed), ECT shows advantages four weeks later but not six months later (Buchan et al., 1992). Relapse rates are also high. But this might not be due to the failure of ECT as a treatment. ECT is rarely incorporated into a broader, ongoing therapeutic strategy, possibly because its dramatic, rapid impact on depressive symptoms obscures the need for follow-up care. This failure to address the sociological or psychological stresses that might have initiated or exacerbated the depression could equally explain the high relapse rates for ECT. Other criticisms include temporary disorientation following ECT, and memory loss that can last for months (indeed, it has been suggested that memory loss is one of the reasons why ECT ‘works’). ECT is now often administered to the right hemisphere only in order to minimize its impact on verbal memories. In addition, up to 33 per cent of patients describe ECT as ‘a very distressing experience’ ( Johnstone, 2003a, p. 239), and there are claims that ECT causes brain damage (Breggin, 1997), although there is no compelling evidence for this.
In contrast, the Royal College of Psychiatrists (1997) views ECT as ‘among the safest medical treatments given under general anaesthesia’ (p. 3) – a view echoed by the psychiatric establishment in many countries. Together with the perceived utility of ECT, these views are likely to ensure its continued use. Antônio Egas Moniz (1874–1955) was born in Portugal and studied neurology in Bordeaux and Paris. He became Chair of Neurology at the University of Coimbra before entering politics, where he served as a deputy in the Portuguese parliament, Minister of Foreign Affairs and Ambassador to Spain. He left politics to return to the University of Lisbon, where, in 1936, he developed the prefrontal leucotomy (also known as frontal lobotomy) as a surgical approach for the radical treatment of several kinds of mental disorder. Moniz was awarded the Nobel Prize for Medicine and Physiology in 1949 for developing this procedure.
PHARMACOTHERAPY – THE ROLE OF MEDICATION
The advent of psychotropic drugs revolutionized the treatment of psychological disorders. By controlling (or at least moderating) the manifestation of some disorders, these drugs have allowed sufferers to be treated without hospitalization. An estimated 90 per cent of patients who see a psychiatrist are prescribed medication (Glenmullen, 2000; Olfson, Pincus & Sabshin, 1994), and general practitioners also frequently prescribe psychotropic medications, especially antidepressants and anxiolytics. So, although they can’t prescribe these drugs themselves (Resnick, 2003), clinical psychologists will have clients who are either taking or in need of medication. This is why knowledge of effective medications, indications for their use, and insight into their side effects is critical for practising clinical psychologists. Antipsychotics – a treatment forschizophrenia The first psychotropic drugs introduced in the 1950s were antipsychotics, which have come to dominate the treatment of schizophrenia. Typical antipsychotics, such as chlorpromazine and haloperidol, reduce psychotic, or so-called ‘positive’ symptoms of schizophrenia (hallucinations and delusions), apparently by blocking dopamine receptors in certain brain systems (see figure 16.4). The stronger the dopamine blockade, the greater the apparent impact on symptoms (Snyder, 1976).
But what of the other, ‘negative’, schizophrenic symptoms – lack of social skills, appropriate affect, motivation and life skills? Atypical antipsychotics, such as clozapine and risperidone, reduce both positive and negative symptoms. These drugs appear to block both dopamine and serotonin receptors, implying a dopamine–serotonin interaction in schizophrenia (though some researchers argue that their effectiveness is due to selective dopamine blockade).
How effective are antipsychotic drugs? The first controlled studies of antipsychotics showed that they were clearly superior to placebos (inactive pills) for improving psychotic symptoms (73 per cent vs. 23 per cent), and subsequent research has replicated this finding. A review of 35 studies shows a similar superiority (16.2 per cent vs. 57.6 per cent) when it comes to relapse (Davis & Andriukaitis, 1986). But antipsychotics neither cure schizophrenia nor alter its progress, and they have potent side effects, including constipation, blurred vision, restlessness and difficulty sitting still (akathisia), cardiac arrhythmia, diminished spontaneity and difficulty initiating usual activities (akinesia). Prolonged treatment can lead to ‘rabbit syndrome’(rapid movement of the lips that mimics the chewing movement of rabbits).
Particularly troubling is that antipsychotics interfere with dopamine systems that control movement. These systems sometimes degenerate in older people, giving rise to Parkinson’s disease, and so this side effect of antipsychotic medication is known as pseudo-parkinsonism. The symptoms are just as real as parkinsonism, and include tremors, drooling, slowed movements, muscular rigidity, difficulty breathing and small handwriting (micrographia). Additional drugs are usually prescribed in schizophrenia to deal with these side effects. Because antipsychotics can mimic neurological disease, they are sometimes referred to as neuroleptics. Prolonged use of antipsychotics can also result in tardive dyskinesia, ‘tardive’ meaning ‘late developing’ and ‘dyskinesia’ meaning ‘disturbance in movement’. This serious disorder is characterized by involuntary movements of the face, trunk or extremities. As a consequence of these side effects and risks, many schizophrenic patients don’t take their medication reliably, resulting in periodic worsening of symptoms and rehospitalizations. In fact, it is not uncommon for people suffering from schizophrenia to become ‘revolving door patients’. Prozac (designed to have a minimal effect on norephinephrine and a maximal effect on serotonin) marked the development of a new class of anti-depressants called selective serotonin reuptake inhibitors (SSRIs). SSRIs have fewer side effects and are much safer to use than tricyclics and MAOIs. An overdose of SSRIs is not as lethal as one involving tricyclics, with MAOIs falling in between the two. This is an important consideration given the increased incidence of suicide attempts in depressed patients. The safety of SSRIs is no doubt one of the factors that has facilitated their widespread use (perhaps over-use) by physicians in general practice. But SSRIs can cause nausea, diarrhoea, insomnia and a loss of sexual desire or response (Montgomery, 1995).
Approximately 70 per cent of patients respond positively to antidepressants, with declines in symptoms apparent within two to six weeks for tricyclics, one to three weeks for MAOIs and two to four weeks for SSRIs (Silver, Yudofsky & Hurowitz, 1994). Patients may do better on one type of antidepressant than another, and sound clinical judgement is needed to find the best antidepressant for each individual. If a patient doesn’t respond to a standard antidepressant, his depression is said to be refractory, and he will most likely be treated with two antidepressants simultaneously. In 1997 a dual-action antidepressant became available, which both blocks serotonin receptors and inhibits its reuptake. Although too early to document its effectiveness, it is likely that this, like other antidepressants, is more than just an antidepressant. This medication has also proven useful in treating panic disorder, eating disorders like bulimia, migraine headache and obsessive– compulsive disorder (Heninger, 1995; Montgomery, 1995).
2 Antimanics People with bipolar disorder are often resistant to taking medication because they miss the ‘high’ experienced in the initial phase of a manic episode. Yet not taking medication is dangerous, because patients often engage in risky behaviours during their manic phase and are at particularly high risk for suicide during the depressive phase.Despite their name, antimanics help to prevent depressive episodes in bipolar disorder (they are also referred to as mood stabilizers). The first antimanic used was lithium carbonate, which remains the treatment of choice for preventing both manic and depressive episodes in bipolar disorder. Acute manic episodes respond to lithium within seven to fourteen days. Because acute mania has the potential to seriously disrupt patients’ lives, a supplemental medication (usually an antipsychotic) is administered in the acute phase of the condition, to bring behaviour under control as soon as possible.
Lithium is effective with about 60–70 per cent of bipolar patients. The mechanism by which it works remains largely unknown (Calabrese & Woyshville, 1995), although it may work by regulating dysfunctional neuronal firing. Patients remain symptom-free for years, provided they keep taking the medication. Commonly occurring side effects are nausea, diarrhoea, excessive urine production, fine hand tremor and fatigue. Because lithium is toxic at high levels, it is a risky treatment when there is a suicide risk involved, and patients need to have their blood levels checked regularly.
Two newer antimanics are anticonvulsant drugs that have been used to treat epilepsy. These drugs – carbamazepine and valproate – often work for bipolar patients who have not responded to lithium. They tend to be tolerated much better by many patients.
Anxiolytics – a treatment for anxiety disorders
Popularly known as tranquillizers, anxiolytics are the most widely used psychotropic drugs. In 1960, a new class of drugs, benzodiazepines, was developed that had a specific effect on anxiety. Some, such as Valium (diazepam), Librium (chlordiazepoxide) and Xanax (alprazolam) have been prescribed so often that they have almost become household words. Benzodiazepines slow nerve cell electrical activity by augmenting the effect of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter.
They are fast acting and can affect anxiety following a single dose. Although useful in treating generalized anxiety disorder, post-traumatic stress disorder, panic disorder and insomnia, they are highly addictive, interact dangerously with alcohol and impair psychomotor performance (so patients are advised to avoid driving during treatment). A newer generation anxiolytic is buspirone, a drug that is chemically distinct from other anxiolytics, is not addictive and does not interact with alcohol or impair psychomotor performance. On the other hand, nausea, headache, insomnia, dizziness and lightheadedness are more common with buspirone. It also has a slow onset action and full therapeutic action takes weeks, making it unsuitable for transient or acute anxiety, where fast relief is needed. Buspirone is as effective as the benzodiazepines in treating generalized anxiety disorder, but less so for panic disorder (Sheehan et al., 1990).In 1962, imipramine, a tricyclic antidepressant, was found to be effective in treating panic attacks. Since then, other antidepressants have been shown to be useful in treating not only panic disorder, but also social phobia and obsessive–compulsive disorder (OCD). But because most OCD patients achieve only a 35–50 per cent decrease in obsessions and compulsions with drug treatment ( Jenike, 1990), they need to undergo psychotherapy at the same time.
ASSESSING THE EFFECTS OF PSYCHOTROPIC DRUGS
Why a whole section on testing drugs for effectiveness? Don’t we simply give the drug to a group of patients and compare their symptoms before and after? This pre–post treatment design seems sensible, but it has many weaknesses. Most obviously, as with any form of therapy, it ignores the possibility that the symptoms may have remitted spontaneously, without the treatment. It also neglects the fact that symptoms of several disorders fluctuate over time. Improvement in the condition may therefore simply reflect spontaneous remission or natural fluctuation rather than any actual drug effect. A control group is critical to assessing the effect of an experimental manipulation – in this case the administration of a drug. When we compare the effect and value of treatment( s) against a control using patients, it is termed a clinical trial. The placebo effect and double-blind procedure So is it sufficient to have two groups of equivalent patients – one receiving the drug and one not? Certainly, in this design, any differences after treatment would not be due to spontaneous remission or the natural course of the disorder, as these factors would affect both groups. But neither could the differences be unequivocally attributed to the drug. We also have to account for the placebo effect – a widely documented phenomenon in the treatment of various diseases from flu to heart disease. It has been shown that up to 70 per cent of patients actually show some real functional improvement after being treated with an inert substance (a placebo) such as a sugar pill. Interestingly, practitioners often make use of the placebo effect in treating patients (Benson & Friedman, 1996). But researchers must eliminate it. Can we do so by simply administering a placebo to our control group, so that they get the same amount of attention and ‘treatment’ as the group treated with the real drug? While this is a dramatic improvement on the basic pre treatment–post treatment design, there is still a problem with this single-blind procedure – so-called because the patient is kept ‘blind’ to the true nature of the treatment. But it is essential that all the patients believe they are receiving real medicine, and this can’t be guaranteed when the administering staff themselves know who is getting the real drug and who is getting the placebo. Even without explicitly revealing the true nature of the treatment to the patient, the knowledge of the staff can subtly influence the patient. It is therefore imperative for all staff who have contact with the patients to remain unaware throughout the study about who is receiving which treatment. This is called a double-blind procedure.
A very powerful experimental technique is the combination of the double-blind procedure with random assignment of patients to treatment condition – randomized clinical trial (RCT). But we still have another couple of problems to overcome. It is unethical to withhold an acceptable treatment in order to administer a placebo, so many RCTs compare the impact of a new drug to treatment as usual. This helps address another problem that sometimes arises with the use of a placebo – side effects can make it apparent to both staff and patients who is receiving the experimental drug. Obvious differences in side effects between treatments tend to be muted when the comparison is with a standard treatment. In RCTs of new drugs, the question is usually one of relative efficacy compared to the currently best available treatment. But even if a new drug is only equivalent to an existing treatment, it may be preferred because of lower cost, or fewer side effects. For example, among antidepressants the newer drugs are generally preferred over older ones, not because they are more effective overall, but because of more acceptable side effects (Thase, 1999). Criteria for effectiveness Finally, we must consider the criteria used to judge the efficacy of a treatment. Usually we look at patient reports and, where possible, ratings by hospital or clinic staff. Assessments by psychologists and medical tests may also be used. But how do we decide if a change is clinically meaningful, rather than simply a statistical measure? This is an important issue that can dramatically alter the inferences we draw about a treatment’s efficacy. For example, suppose reports from depressed patients are statistically different from a comparison group after treatment, and yet these same patients show little difference in their ability to function in everyday life and remain severely depressed. One way to address this issue is to test whether patient self-reports fall into the non-depressed range of scores. Another method that can be used is to apply more nov el statistical techniques such as comparing the ‘effect size’ underlying the statistical difference. A further criterion that is increasingly emphasized is the cost-effectiveness of a treatment. So we might ask whether a new treatment for drug dependence leads to fewer arrests and days in prison, or whether a new antidepressant leads to fewer lost work days, and so on. In economically difficult times, care is sometimes subordinated to cost, making the use of psychotropic drugs particularly attractive for the treatment of psychological disorders. The fact that they are often fast acting only adds to their appeal (although, as we have seen, the duration of these beneficial effects may be a quite different matter – we explore this question further in the next section). The limits of drug therapy There is no doubt that modern psychotropic drugs have revolutionized the treatment of psychological disorders and restored the lives of many sufferers. No one should be treated for schizophrenia or bipolar disorder without suitable medication being available, and drugs can be appropriate for many other psychological disorders too. And yet the use of psychotropic drugs is controversial, with some asserting that the beneficial effects are quite limited (Fisher & Greenberg, 1989). Others have raised concerns about over-use (Olfson et al., 1998), abuse (especially regarding anxiolytics such as valium) and possible addiction. Furthermore, some researchers have argued that the impact of psychotropic drugs largely reflects a placebo effect (Kirsch & Sapirstein, 1998).
In any event, drug treatments have some obvious limits:
1. Not everyone responds to the drug.
2. Side effects may preclude their use for some patients, and may lead others to discontinue their use – a particularly important consideration for treatments like antipsychotics and antimanics, when ongoing maintenance doses are needed to control symptoms effectively.
3. Drug treatment does nothing to help patients learn how to cope with life experiences that may have contributed to the disorder in the first place.
This leads us neatly into the essential role of psychological treatments.
Until the late eighteenth century, people suffering from a psychological disorder were thought to be possessed by demons or evil spirits. Treatment was designed to alter the body in order to let out the spirits or make it an inhospitable habitat for them. Among the earliest biological treatments was ‘trepanning’, or removing part of the skull bone to allow evil spirits out of the body – a practice that endured until the twentieth century. Numerous other equally unpleasant biological assaults on the afflicted included bloodletting, beatings, purgatives and immersion in water to the point of near drowning. With the demise of witchcraft, people with psychological disorders came to be seen as ill, and the traditional methods of medicine began to be applied to them. But until the advent of the twentieth century, medical treatments were little different from the methods used to drive out evil spirits and were equally unsuccessful.
PSYCHOSURGERY AND ECT
Psychosurgery
Psychosurgery involves severing or otherwise disabling areas of the brain to treat a psychological disorder in the absence of any clear organic cause. Its use was triggered by research on chimpanzees that demonstrated the role of the temporal and frontal cortex in the control of emotional behaviour and aggression. Antônio Egas Moniz, of the University of Lisbon Medical School, developed a procedure in which the nerve fibres connecting the frontal lobe with other parts of the brain were cut. The prefrontal lobotomy became particularly popular in the USA, where a simple technique (that came to be known as ‘ice pick’ surgery) was administered during an outpatient visit (see figure 16.1). As a result, over 50,000 lobotomies had been performed in the United States by the mid 1950s (Cosgrove, 2000).The lobotomy has been replaced by the cingulotomy,in which neurosurgeons make lesions in the cingulate gyrus,a section of the brain connecting the prefrontal cortex to the limbic system (brain structures involved in autonomic body functions and some emotion and behaviour . Baer and colleagues (1995) found that this procedure,which had few side effects, successfully decreased anxiety andobsessive behaviour. But recent studies demonstrate that cingulotomy produces substantial benefits in only about a third of patients (Cosgrove, 2000).Although the number of psychosurgeries performed worldwide today isn’t known, it is estimated that fewer than 25 occur annually in Britain and the United States, about five a year in Sweden and one or two in Australia. Only people with very severe, disabling psychological disorders that resist other forms of treatment are even considered for psychosurgery today.Electroconvulsive therapy Another controversial treatment, and one that is still used fairly widely, is electroconvulsive therapy (ECT). In England 11,340 patients received ECT in 1999 (Department of Health, 1999).
Two electrodes are placed on the scalp and a moderately intense electric current is passed
between them for about half a second. This produces a 30- to 60- second seizure, similar to those experienced by epileptics. Today, short-acting anaesthetics and muscle relaxants are given prior to ECT, reducing the seizure to a few visible twitches. The usual course involves between four and twelve treatments over a oneor two-week period. ECT was initiated in the 1930s to treat schizophrenia, in the mistaken belief that epilepsy and schizophrenia are incompatible. It proved to be an ineffective treatment for schizophrenia but isnow widely believed to be effective in treating severe depression (Royal College of Psychiatrists, 1995). It is often used to treat depressed people who have not responded to antidepressant medication, can’t take medication because of the risk of suicide or other medical considerations, or risk death through refusal to eat.
Despite claims of ‘marked improvement . . . in 80% to 90% of patients’ (Silver, Yudovsky & Hurowitz, 1994, p. 983), the case for ECT is far from clear-cut. The consensus from clinical practice is that it can have beneficial effects, but research shows that the effects are relatively short-term. For example, compared to a sham treatment (i.e. the same procedure but with no current passed), ECT shows advantages four weeks later but not six months later (Buchan et al., 1992). Relapse rates are also high. But this might not be due to the failure of ECT as a treatment. ECT is rarely incorporated into a broader, ongoing therapeutic strategy, possibly because its dramatic, rapid impact on depressive symptoms obscures the need for follow-up care. This failure to address the sociological or psychological stresses that might have initiated or exacerbated the depression could equally explain the high relapse rates for ECT. Other criticisms include temporary disorientation following ECT, and memory loss that can last for months (indeed, it has been suggested that memory loss is one of the reasons why ECT ‘works’). ECT is now often administered to the right hemisphere only in order to minimize its impact on verbal memories. In addition, up to 33 per cent of patients describe ECT as ‘a very distressing experience’ ( Johnstone, 2003a, p. 239), and there are claims that ECT causes brain damage (Breggin, 1997), although there is no compelling evidence for this.
In contrast, the Royal College of Psychiatrists (1997) views ECT as ‘among the safest medical treatments given under general anaesthesia’ (p. 3) – a view echoed by the psychiatric establishment in many countries. Together with the perceived utility of ECT, these views are likely to ensure its continued use. Antônio Egas Moniz (1874–1955) was born in Portugal and studied neurology in Bordeaux and Paris. He became Chair of Neurology at the University of Coimbra before entering politics, where he served as a deputy in the Portuguese parliament, Minister of Foreign Affairs and Ambassador to Spain. He left politics to return to the University of Lisbon, where, in 1936, he developed the prefrontal leucotomy (also known as frontal lobotomy) as a surgical approach for the radical treatment of several kinds of mental disorder. Moniz was awarded the Nobel Prize for Medicine and Physiology in 1949 for developing this procedure.
PHARMACOTHERAPY – THE ROLE OF MEDICATION
The advent of psychotropic drugs revolutionized the treatment of psychological disorders. By controlling (or at least moderating) the manifestation of some disorders, these drugs have allowed sufferers to be treated without hospitalization. An estimated 90 per cent of patients who see a psychiatrist are prescribed medication (Glenmullen, 2000; Olfson, Pincus & Sabshin, 1994), and general practitioners also frequently prescribe psychotropic medications, especially antidepressants and anxiolytics. So, although they can’t prescribe these drugs themselves (Resnick, 2003), clinical psychologists will have clients who are either taking or in need of medication. This is why knowledge of effective medications, indications for their use, and insight into their side effects is critical for practising clinical psychologists. Antipsychotics – a treatment forschizophrenia The first psychotropic drugs introduced in the 1950s were antipsychotics, which have come to dominate the treatment of schizophrenia. Typical antipsychotics, such as chlorpromazine and haloperidol, reduce psychotic, or so-called ‘positive’ symptoms of schizophrenia (hallucinations and delusions), apparently by blocking dopamine receptors in certain brain systems (see figure 16.4). The stronger the dopamine blockade, the greater the apparent impact on symptoms (Snyder, 1976).
But what of the other, ‘negative’, schizophrenic symptoms – lack of social skills, appropriate affect, motivation and life skills? Atypical antipsychotics, such as clozapine and risperidone, reduce both positive and negative symptoms. These drugs appear to block both dopamine and serotonin receptors, implying a dopamine–serotonin interaction in schizophrenia (though some researchers argue that their effectiveness is due to selective dopamine blockade).
How effective are antipsychotic drugs? The first controlled studies of antipsychotics showed that they were clearly superior to placebos (inactive pills) for improving psychotic symptoms (73 per cent vs. 23 per cent), and subsequent research has replicated this finding. A review of 35 studies shows a similar superiority (16.2 per cent vs. 57.6 per cent) when it comes to relapse (Davis & Andriukaitis, 1986). But antipsychotics neither cure schizophrenia nor alter its progress, and they have potent side effects, including constipation, blurred vision, restlessness and difficulty sitting still (akathisia), cardiac arrhythmia, diminished spontaneity and difficulty initiating usual activities (akinesia). Prolonged treatment can lead to ‘rabbit syndrome’(rapid movement of the lips that mimics the chewing movement of rabbits).
Particularly troubling is that antipsychotics interfere with dopamine systems that control movement. These systems sometimes degenerate in older people, giving rise to Parkinson’s disease, and so this side effect of antipsychotic medication is known as pseudo-parkinsonism. The symptoms are just as real as parkinsonism, and include tremors, drooling, slowed movements, muscular rigidity, difficulty breathing and small handwriting (micrographia). Additional drugs are usually prescribed in schizophrenia to deal with these side effects. Because antipsychotics can mimic neurological disease, they are sometimes referred to as neuroleptics. Prolonged use of antipsychotics can also result in tardive dyskinesia, ‘tardive’ meaning ‘late developing’ and ‘dyskinesia’ meaning ‘disturbance in movement’. This serious disorder is characterized by involuntary movements of the face, trunk or extremities. As a consequence of these side effects and risks, many schizophrenic patients don’t take their medication reliably, resulting in periodic worsening of symptoms and rehospitalizations. In fact, it is not uncommon for people suffering from schizophrenia to become ‘revolving door patients’. Prozac (designed to have a minimal effect on norephinephrine and a maximal effect on serotonin) marked the development of a new class of anti-depressants called selective serotonin reuptake inhibitors (SSRIs). SSRIs have fewer side effects and are much safer to use than tricyclics and MAOIs. An overdose of SSRIs is not as lethal as one involving tricyclics, with MAOIs falling in between the two. This is an important consideration given the increased incidence of suicide attempts in depressed patients. The safety of SSRIs is no doubt one of the factors that has facilitated their widespread use (perhaps over-use) by physicians in general practice. But SSRIs can cause nausea, diarrhoea, insomnia and a loss of sexual desire or response (Montgomery, 1995).
Approximately 70 per cent of patients respond positively to antidepressants, with declines in symptoms apparent within two to six weeks for tricyclics, one to three weeks for MAOIs and two to four weeks for SSRIs (Silver, Yudofsky & Hurowitz, 1994). Patients may do better on one type of antidepressant than another, and sound clinical judgement is needed to find the best antidepressant for each individual. If a patient doesn’t respond to a standard antidepressant, his depression is said to be refractory, and he will most likely be treated with two antidepressants simultaneously. In 1997 a dual-action antidepressant became available, which both blocks serotonin receptors and inhibits its reuptake. Although too early to document its effectiveness, it is likely that this, like other antidepressants, is more than just an antidepressant. This medication has also proven useful in treating panic disorder, eating disorders like bulimia, migraine headache and obsessive– compulsive disorder (Heninger, 1995; Montgomery, 1995).
2 Antimanics People with bipolar disorder are often resistant to taking medication because they miss the ‘high’ experienced in the initial phase of a manic episode. Yet not taking medication is dangerous, because patients often engage in risky behaviours during their manic phase and are at particularly high risk for suicide during the depressive phase.Despite their name, antimanics help to prevent depressive episodes in bipolar disorder (they are also referred to as mood stabilizers). The first antimanic used was lithium carbonate, which remains the treatment of choice for preventing both manic and depressive episodes in bipolar disorder. Acute manic episodes respond to lithium within seven to fourteen days. Because acute mania has the potential to seriously disrupt patients’ lives, a supplemental medication (usually an antipsychotic) is administered in the acute phase of the condition, to bring behaviour under control as soon as possible.
Lithium is effective with about 60–70 per cent of bipolar patients. The mechanism by which it works remains largely unknown (Calabrese & Woyshville, 1995), although it may work by regulating dysfunctional neuronal firing. Patients remain symptom-free for years, provided they keep taking the medication. Commonly occurring side effects are nausea, diarrhoea, excessive urine production, fine hand tremor and fatigue. Because lithium is toxic at high levels, it is a risky treatment when there is a suicide risk involved, and patients need to have their blood levels checked regularly.
Two newer antimanics are anticonvulsant drugs that have been used to treat epilepsy. These drugs – carbamazepine and valproate – often work for bipolar patients who have not responded to lithium. They tend to be tolerated much better by many patients.
Anxiolytics – a treatment for anxiety disorders
Popularly known as tranquillizers, anxiolytics are the most widely used psychotropic drugs. In 1960, a new class of drugs, benzodiazepines, was developed that had a specific effect on anxiety. Some, such as Valium (diazepam), Librium (chlordiazepoxide) and Xanax (alprazolam) have been prescribed so often that they have almost become household words. Benzodiazepines slow nerve cell electrical activity by augmenting the effect of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter.
They are fast acting and can affect anxiety following a single dose. Although useful in treating generalized anxiety disorder, post-traumatic stress disorder, panic disorder and insomnia, they are highly addictive, interact dangerously with alcohol and impair psychomotor performance (so patients are advised to avoid driving during treatment). A newer generation anxiolytic is buspirone, a drug that is chemically distinct from other anxiolytics, is not addictive and does not interact with alcohol or impair psychomotor performance. On the other hand, nausea, headache, insomnia, dizziness and lightheadedness are more common with buspirone. It also has a slow onset action and full therapeutic action takes weeks, making it unsuitable for transient or acute anxiety, where fast relief is needed. Buspirone is as effective as the benzodiazepines in treating generalized anxiety disorder, but less so for panic disorder (Sheehan et al., 1990).In 1962, imipramine, a tricyclic antidepressant, was found to be effective in treating panic attacks. Since then, other antidepressants have been shown to be useful in treating not only panic disorder, but also social phobia and obsessive–compulsive disorder (OCD). But because most OCD patients achieve only a 35–50 per cent decrease in obsessions and compulsions with drug treatment ( Jenike, 1990), they need to undergo psychotherapy at the same time.
ASSESSING THE EFFECTS OF PSYCHOTROPIC DRUGS
Why a whole section on testing drugs for effectiveness? Don’t we simply give the drug to a group of patients and compare their symptoms before and after? This pre–post treatment design seems sensible, but it has many weaknesses. Most obviously, as with any form of therapy, it ignores the possibility that the symptoms may have remitted spontaneously, without the treatment. It also neglects the fact that symptoms of several disorders fluctuate over time. Improvement in the condition may therefore simply reflect spontaneous remission or natural fluctuation rather than any actual drug effect. A control group is critical to assessing the effect of an experimental manipulation – in this case the administration of a drug. When we compare the effect and value of treatment( s) against a control using patients, it is termed a clinical trial. The placebo effect and double-blind procedure So is it sufficient to have two groups of equivalent patients – one receiving the drug and one not? Certainly, in this design, any differences after treatment would not be due to spontaneous remission or the natural course of the disorder, as these factors would affect both groups. But neither could the differences be unequivocally attributed to the drug. We also have to account for the placebo effect – a widely documented phenomenon in the treatment of various diseases from flu to heart disease. It has been shown that up to 70 per cent of patients actually show some real functional improvement after being treated with an inert substance (a placebo) such as a sugar pill. Interestingly, practitioners often make use of the placebo effect in treating patients (Benson & Friedman, 1996). But researchers must eliminate it. Can we do so by simply administering a placebo to our control group, so that they get the same amount of attention and ‘treatment’ as the group treated with the real drug? While this is a dramatic improvement on the basic pre treatment–post treatment design, there is still a problem with this single-blind procedure – so-called because the patient is kept ‘blind’ to the true nature of the treatment. But it is essential that all the patients believe they are receiving real medicine, and this can’t be guaranteed when the administering staff themselves know who is getting the real drug and who is getting the placebo. Even without explicitly revealing the true nature of the treatment to the patient, the knowledge of the staff can subtly influence the patient. It is therefore imperative for all staff who have contact with the patients to remain unaware throughout the study about who is receiving which treatment. This is called a double-blind procedure.
A very powerful experimental technique is the combination of the double-blind procedure with random assignment of patients to treatment condition – randomized clinical trial (RCT). But we still have another couple of problems to overcome. It is unethical to withhold an acceptable treatment in order to administer a placebo, so many RCTs compare the impact of a new drug to treatment as usual. This helps address another problem that sometimes arises with the use of a placebo – side effects can make it apparent to both staff and patients who is receiving the experimental drug. Obvious differences in side effects between treatments tend to be muted when the comparison is with a standard treatment. In RCTs of new drugs, the question is usually one of relative efficacy compared to the currently best available treatment. But even if a new drug is only equivalent to an existing treatment, it may be preferred because of lower cost, or fewer side effects. For example, among antidepressants the newer drugs are generally preferred over older ones, not because they are more effective overall, but because of more acceptable side effects (Thase, 1999). Criteria for effectiveness Finally, we must consider the criteria used to judge the efficacy of a treatment. Usually we look at patient reports and, where possible, ratings by hospital or clinic staff. Assessments by psychologists and medical tests may also be used. But how do we decide if a change is clinically meaningful, rather than simply a statistical measure? This is an important issue that can dramatically alter the inferences we draw about a treatment’s efficacy. For example, suppose reports from depressed patients are statistically different from a comparison group after treatment, and yet these same patients show little difference in their ability to function in everyday life and remain severely depressed. One way to address this issue is to test whether patient self-reports fall into the non-depressed range of scores. Another method that can be used is to apply more nov el statistical techniques such as comparing the ‘effect size’ underlying the statistical difference. A further criterion that is increasingly emphasized is the cost-effectiveness of a treatment. So we might ask whether a new treatment for drug dependence leads to fewer arrests and days in prison, or whether a new antidepressant leads to fewer lost work days, and so on. In economically difficult times, care is sometimes subordinated to cost, making the use of psychotropic drugs particularly attractive for the treatment of psychological disorders. The fact that they are often fast acting only adds to their appeal (although, as we have seen, the duration of these beneficial effects may be a quite different matter – we explore this question further in the next section). The limits of drug therapy There is no doubt that modern psychotropic drugs have revolutionized the treatment of psychological disorders and restored the lives of many sufferers. No one should be treated for schizophrenia or bipolar disorder without suitable medication being available, and drugs can be appropriate for many other psychological disorders too. And yet the use of psychotropic drugs is controversial, with some asserting that the beneficial effects are quite limited (Fisher & Greenberg, 1989). Others have raised concerns about over-use (Olfson et al., 1998), abuse (especially regarding anxiolytics such as valium) and possible addiction. Furthermore, some researchers have argued that the impact of psychotropic drugs largely reflects a placebo effect (Kirsch & Sapirstein, 1998).
In any event, drug treatments have some obvious limits:
1. Not everyone responds to the drug.
2. Side effects may preclude their use for some patients, and may lead others to discontinue their use – a particularly important consideration for treatments like antipsychotics and antimanics, when ongoing maintenance doses are needed to control symptoms effectively.
3. Drug treatment does nothing to help patients learn how to cope with life experiences that may have contributed to the disorder in the first place.
This leads us neatly into the essential role of psychological treatments.
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