Ever since someone discovered that a whack to the head can affect the mind, people have suspected that direct brain interventions might hold the keys to a cure for psychological disorders. Archaeological evidence, for example, indicates that the occasional human thousands of years ago was “treated” for some malady by the practice of trephining (drilling a hole in the skull), perhaps in the belief that this would release evil spirits that were affecting the mind (Alt et al., 1997). Surgery for psychological disorders is a last resort nowadays, and treatments that focus on the brain usually involve interventions that are less dramatic. The use of drugs to influence the brain was also discovered in prehistory (alcohol, for example, has been around for a long time). Since then, drug treatments have grown in variety, effectiveness, and popularity and they are now the most common medical approach in treating psychological disorders (see FIGURE 16.2).

The story of drug treatments for severe psychological disorders starts in the 1950s, with chlorpromazine (brand name Thorazine), which was originally developed as a sedative, but when administered to people with schizophrenia, often left them euphoric and docile, although they had formerly been agitated and incorrigible (Barondes, 2003). Chlorpromazine was the first in a series of antipsychotic drugs, which treat schizophrenia and related psychotic disorders, and completely changed the way schizophrenia was managed. Other related medications, such as thioridazine (Mellaril) and haloperidol (Haldol), followed. Before the introduction of antipsychotic drugs, people with schizophrenia often exhibited bizarre symptoms and were sometimes so disruptive and difficult to manage that the only way to protect them (and other people) was to keep them in hospitals for people with mental disorders, which were initially called asylums but now are referred to as psychiatric hospitals (see The Real World box: Treating Severe Mental Disorders). In the period following the introduction of these drugs, the number of people in psychiatric hospitals decreased by more than two thirds. Antipsychotic drugs made possible the deinstitutionalization of hundreds of thousands of people and gave a major boost to the field of psychopharmacology, the study of drug effects on psychological states and symptoms.

647

648

Antipsychotic medications are believed to block dopamine receptors in parts of the brain such as the mesolimbic area, an area between the tegmentum (in the midbrain) and various subcortical structures (see the Neuroscience and Behaviour chapter). The medication reduces dopamine activity in these areas. The effectiveness of schizophrenia medications led to the dopamine hypothesis (described in the Psychological Disorders chapter), suggesting that schizophrenia may be caused by excess dopamine in the synapse. Research has indeed found that dopamine overactivity in the mesolimbic area of the brain is related to the more bizarre positive symptoms of schizophrenia, such as hallucinations and delusions (Marangell et al., 2003).

Although antipsychotic drugs work well for positive symptoms, it turns out that negative symptoms of schizophrenia, such as emotional numbing and social withdrawal, may be related to dopamine underactivity in the mesocortical areas of the brain (connections between parts of the tegmentum and the cortex). This may help explain why antipsychotic medications do not relieve negative symptoms well. Instead of a medication that blocks dopamine receptors, negative symptoms require a medication that increases the amount of dopamine available at the synapse. This is a good example of how medical treatments can have broad psychological effects but not target specific psychological symptoms.

After the introduction of antipsychotic medications, there was little change in the available treatments for schizophrenia for more than a quarter of a century. However, in the 1990s, a new class of antipsychotic drugs was introduced. These newer drugs, which include clozapine (Clozaril), risperidone (Risperidal), and olanzepine (Zyprexa), have become known as atypical antipsychotics (the older drugs are now often referred to as conventional or typical antipsychotics). Unlike the older antipsychotic medications, these newer drugs appear to affect both the dopamine and serotonin systems, blocking both types of receptors. The ability to block serotonin receptors appears to be a useful addition because enhanced serotonin activity in the brain has been implicated in some of the core difficulties in schizophrenia, such as cognitive and perceptual disruptions, as well as mood disturbances. This may explain why atypical antipsychotics work at least as well as older drugs for the positive symptoms of schizophrenia and also work fairly well for the negative symptoms (Bradford, Stroup, & Lieberman, 2002).

Like most medications, antipsychotic drugs have side effects. The side effects can be sufficiently unpleasant that some people “go off their meds,” preferring their symptoms to the drug. One side effect that often occurs with long-term use is tardive dyskinesia, a condition of involuntary movements of the face, mouth, and extremities. In fact, people often need to take another medication to treat the unwanted side effects of the conventional antipsychotic drugs. Side effects of the newer medications tend to be different and sometimes milder than those of the older antipsychotics. For that reason, the atypical antipsychotics are now usually the front-line treatments for schizophrenia (Meltzer, 2013).

649

Anti-anxiety medications are drugs that help reduce a person’s experience of fear or anxiety. The most commonly used antianxiety medications are the benzodiazepines, a type of tranquilizer that works by facilitating the action of the neurotransmitter gamma-aminobutyric acid (GABA). As you read in the Neuroscience and Behaviour chapter, GABA inhibits certain neurons in the brain. This inhibitory action can produce a calming effect for the person. Commonly prescribed benzodiazepines include diazepam (Valium), lorazepam (Ativan), and alprazolam (Xanax). The benzodiazepines typically take effect in a matter of minutes and are effective for reducing symptoms of anxiety disorders (Roy-Byrne & Cowley, 2002).

Nonetheless, these days doctors are relatively cautious when prescribing benzodiazepines. One concern is that these drugs have the potential for abuse. They are often associated with the development of drug tolerance, which is the need for higher dosages over time to achieve the same effects following long-term use (see the Consciousness chapter). Furthermore, after people become tolerant of the drug, they risk significant withdrawal symptoms when it is discontinued. Some withdrawal symptoms include increased heart rate, shakiness, insomnia, agitation, and anxiety—the very symptoms the drug was taken to eliminate! Therefore, people who take benzodiazepines for extended periods may have difficulty coming off these drugs and should discontinue their medications gradually to minimize withdrawal symptoms (Schatzberg, Cole, & DeBattista, 2003). Another consideration when prescribing benzodiazepines is their side effects. The most common side effect is drowsiness, although benzodiazepines can also have negative effects on coordination and memory. And, benzodiazapines combined with alcohol can depress respiration, potentially causing accidental death.

When anxiety leads to insomnia, drugs known as hypnotics may be useful as sleep aids. One such drug, zolpidem (Ambien), is in wide use and is often effective, but with some reports of sleepwalking, sleep-eating, and even sleep-driving (Hughes, 2007). Another alternative for anxiety is buspirone (Buspar), which has been shown to reduce anxiety among individuals who suffer from generalized anxiety disorder (Roy-Byrne & Cowley, 2002).

Antidepressants are a class of drugs that help lift people’s moods. They were first introduced in the 1950s, when iproniazid, a drug that was used to treat tuberculosis, was found to elevate mood (Selikoff, Robitzek, & Ornstein, 1952). Iproniazid is a monoamine oxidase inhibitor (MAOI), a medication that prevents the enzyme monoamine oxidase from breaking down neurotransmitters such as norepinephrine, serotonin, and dopamine. However, despite their effectiveness, MAOIs are rarely prescribed anymore. MAOI side effects such as dizziness and loss of sexual interest are often difficult to tolerate, and these drugs interact with many different medications, including over-the-counter cold medicines. They also can cause dangerous increases in blood pressure when taken with foods that contain tyramine, a natural substance formed from the breakdown of protein in certain cheeses, beans, aged meats, soy products, and draft beer.

A second category of antidepressants is the tricyclic antidepressants, which were also introduced in the 1950s. These include drugs such as imipramine (Tofranil) and amitriptyline (Elavil). These medications block the reuptake of norepinephrine and serotonin, thereby increasing the amount of neurotransmitter in the synaptic space between neurons. The most common side effects of tricyclic antidepressants include dry mouth, constipation, difficulty urinating, blurred vision, and racing heart (Marangell et al., 2003). Although these drugs are still prescribed, they are used much less frequently than they were in the past because of these side effects.

650

Among the most commonly used antidepressants today are the selective serotonin reuptake inhibitors, or SSRIs, which include drugs such as fluoxetine (Prozac), citalopram (Celexa), and paroxetine (Paxil). The SSRIs work by blocking the reuptake of serotonin in the brain, which makes more serotonin available in the synaptic space between neurons. The greater availability of serotonin in the synapse gives the neuron a better chance of “recognizing” and using this neurotransmitter in sending the desired signal. The SSRIs were developed based on hypotheses that low levels of serotonin are a causal factor in depression. Supporting this hypothesis, SSRIs are effective for depression, as well as for a wide range of other problems. SSRIs are called selective because, unlike the tricyclic antidepressants, which work on the serotonin and norepinephrine systems, SSRIs work more specifically on the serotonin system (see FIGURE 16.3).

Finally, antidepressants such as Effexor (venlafaxine) and Wellbutrin (ibupropion) offer other alternatives. Effexor is an example of a serotonin and norepinephrine reuptake inhibitor (SNRI); whereas SSRIs act only upon serotonin, SNRIs act on both serotonin and norepinephrine. Wellbutrin, in contrast, is a norepinephrine and dopamine reuptake inhibitor. These and other newly developed antidepressants appear to have fewer (or at least different) side effects than the tricyclic antidepressants and MAOIs.

Most antidepressants can take up to a month before they start to have an effect on mood. Besides relieving symptoms of depression, almost all of the antidepressants effectively treat anxiety disorders, and many of them can resolve other problems, such as eating disorders. In fact, several companies that manufacture SSRIs have marketed their drugs as treatments for anxiety disorders rather than for their antidepressant effects. Although antidepressants can be effective in treating major depression, they are not recommended for treating bipolar disorder, which is characterized by manic or hypomanic episodes (see the Psychological Disorders chapter). Antidepressants are not prescribed because, in the process of lifting one’s mood, they might actually trigger a manic episode in a person with bipolar disorder. Instead, bipolar disorder is treated with mood stabilizers, which are medications used to suppress swings between mania and depression. Commonly used mood stabilizers include lithium and valproate. Even in unipolar depression, lithium is sometimes effective when combined with traditional antidepressants in people who do not respond to antidepressants alone.

651

Lithium has been associated with possible long-term kidney and thyroid problems, so people taking lithium must monitor their blood levels of lithium on a regular basis. Furthermore, lithium has a precise range in which it is useful for each person, another reason it should be closely monitored with blood tests. Valproate, in contrast, does not require such careful blood monitoring. Although valproate may have side effects, it is currently the most commonly prescribed drug in the United States for bipolar disorder (Schatzberg et al., 2003). In sum, although the antidepressants are effective for a wide variety of problems, mood stabilizers may be required when a person’s symptoms include extreme swings between highs and lows, such as experienced with bipolar disorder.

In a survey of more than 18 000 Canadians 45 years old and over, approximately 15 percent reported using alternative “medications” such as herbal medicines, megavitamins, homeopathic remedies, or naturopathic remedies to treat anxiety and depression (Crabb & Hunsley, 2011). Major reasons people use these products are that they are easily available over the counter, are less expensive, and are perceived as “natural” alternatives to synthetic or manmade “drugs.” Are herbal and natural products effective in treating mental health problems, or are they just “snake oil?”

The answer to this question is not simple. Currently, herbal products are not considered medications by regulatory agencies like Health Canada, so they are exempt from rigorous research to establish their safety and effectiveness. Instead, herbal products are classified as nutritional supplements and regulated in the same way as food. There is little scientific information about herbal products, including possible interactions with other medications, possible tolerance and withdrawal symptoms, side effects, appropriate dosages, how they work, or even whether they work—and the purity of these products often varies from brand to brand (Jordan, Cunningham, & Marles, 2010).

There is research support for the effectiveness of some herbal and natural products, but the evidence is not overwhelming (Lake, 2009). Products such as inositol (a bran derivative), kava (an herb related to black pepper), omega-3 fatty acid (a fish oil), and SAM-e (an amino acid derivative) are sold as health foods and are described as having positive psychological effects of various kinds, but the evidence is mixed. For example, in the case of St. John’s wort (a wort, it turns out, is an herb), some studies have shown it has an advantage over a placebo condition (e.g., Lecrubier et al., 2002) for the treatment of depression, whereas others show no advantage (e.g., Hypericum Depression Trial Study Group, 2002). Omega-3 fatty acids have been linked with lower rates of depression and suicide, and several treatment studies have repeatedly shown that omega-3s are superior to placebo at decreasing depression (see FIGURE 16.4) (Lewis et al., 2011; Parker, Gibson, et al., 2006). Overall, although herbal medications and treatments are worthy of continued research, these products should be closely monitored and used judiciously until more is known about their safety and effectiveness.

652

Given that psychological treatments and medications have both shown an ability to treat mental disorders effectively, some natural next questions are: Which is more effective? Is the combination of psychological and medicinal treatments better than either by itself? Many studies have compared psychological treatments, medication, and combinations of these approaches for addressing psychological disorders. The results of these studies often depend on the particular problem being considered. For example, in the cases of schizophrenia and bipolar disorder, researchers have found that medication is more effective than psychological treatment and so is considered a necessary part of treatment; recent studies have tended to examine whether adding psychotherapeutic treatments such as social skills training or cognitive behavioural treatment can be helpful (they can). In the case of mood and anxiety disorders, medication and psychological treatments are equally effective. One study compared cognitive behaviour therapy, imipramine (the antidepressant also known as Tofranil), and the combination of these treatments (CBT plus imipramine) with a placebo (administration of an inert medication) for the treatment of panic disorder (Barlow et al., 2000). After 12 weeks of treatment, either CBT alone or imipramine alone was found to be superior to a placebo. For the CBT plus imipramine condition, the response rate also exceeded the rate for the placebo, but was not significantly better than that for either CBT or imipramine alone. In other words, either treatment was better than nothing, but the combination of treatments was not significantly more effective than one or the other (see FIGURE 16.5). More is not always better.

653

654

Given that both therapy and medications are effective, one question is whether they work through similar mechanisms. A study of people with social phobia examined patterns of cerebral blood flow following treatment using either citalopram (an SSRI) or CBT (Furmark et al., 2002). Participants in both groups were alerted to the possibility that they would soon have to speak in public. In both groups, those who responded to treatment showed similar reductions in activation in the amygdala, hippocampus, and neighbouring cortical areas during this challenge (see FIGURE 16.6). The amygdala, located next to the hippocampus (see Figure 6.18) plays a significant role in memory for emotional information. These findings suggest that both therapy and medication affect the brain in regions associated with a reaction to threat. Although it might seem that events that influence the brain should be physical—after all, the brain is a physical object—it is important to keep in mind that environmental learning experiences, such as psychological treatment, produce similar influences on the brain.

One complication in combining medication and psychotherapy is that these treatments are often provided by different people. Psychiatrists are trained in the administration of medication in medical school (and they may also provide psychological treatment), whereas psychologists provide psychological treatment but not medication. This means that the coordination of treatment often requires cooperation between psychologists and psychiatrists.

The question of whether psychologists should be licensed to prescribe medications has been a source of debate among psychologists and physicians (Fox et al., 2009). Opponents argue that psychologists do not have the medical training to understand how medications interact with other drugs. Proponents of prescription privileges argue that patient safety would not be compromised as long as rigorous training procedures were established. This issue remains a focus of debate, and at present, the coordination of medication and psychological treatment usually involves a team effort of psychiatry and psychology.

Medication can be an effective biological treatment, but for some people medications do not work or side effects are intolerable. If this group of people does not respond to psychotherapy either, what other options do they have to achieve symptom relief? Some additional avenues of help are available, but some are risky or poorly understood.

One commonly used biological treatment for severe mental disorders is electroconvulsive therapy (ECT), sometimes referred to as shock therapy, which is a treatment that involves inducing a brief seizure by delivering an electrical shock to the brain. The shock is applied to the person’s scalp for less than a second. ECT is primarily used to treat severe depression that has not responded to antidepressant medications, although it may also be useful for treating bipolar disorder (Khalid et al., 2008; Poon et al., 2012). Patients are pretreated with muscle relaxants and are under general anesthetic, so they are not conscious of the procedure. The main side effect of ECT is impaired short-term memory, which usually improves over the first month or two after the end of treatment. In addition, patients undergoing this procedure sometimes report headaches and muscle aches afterward (Marangell et al., 2003). Despite these side effects, the treatment can be effective: ECT is more effective than simulated ECT, placebo, and antidepressant drugs such as tricyclics and MAOIs (Pagnin et al., 2008).

655

Another biological approach that does not involve medication is transcranial magnetic stimulation (TMS), a treatment that involves placing a powerful pulsed magnet over a person’s scalp, which alters neuronal activity in the brain. As a treatment for depression, the magnet is placed just above the right or left eyebrow in an effort to stimulate the right or left prefrontal cortex (areas of the brain implicated in depression). TMS is an exciting development because it is noninvasive and has fewer side effects than ECT (see the Neuroscience and Behaviour chapter). Side effects are minimal; they include mild headache and a small risk of seizure, but TMS has no impact on memory or concentration. TMS may be particularly useful in treating depression that is unresponsive to medication (Avery et al., 2009). In fact, a study comparing TMS to ECT found that both procedures were effective, with no significant differences between them (Janicak et al., 2002). Other studies have found that TMS can also be used to treat auditory hallucinations in schizophrenia (Aleman, Sommer, & Kahn, 2007).

Phototherapy, a therapy that involves repeated exposure to bright light, may be helpful to people who have a seasonal pattern to their depression. This could include people suffering with seasonal affective disorder (SAD) (see the Psychological Disorders chapter), or those who experience depression only in the winter months due to the lack of sunlight. Typically, people are exposed to bright light in the morning, using a lamp designed for this purpose. Phototherapy has not been as well researched as psychological treatment or medication, but the handful of studies available suggest it is approximately as effective as antidepressant medication in the treatment of SAD (Thaler et al., 2011).

In very rare cases, psychosurgery, the surgical destruction of specific brain areas, may be used to treat psychological disorders. Psychosurgery has a controversial history, beginning in the 1930s with the invention of the lobotomy by Portuguese physician Egas Moniz (1874–1955). After discovering that certain surgical procedures on animal brains calmed behaviour, Moniz began to use similar techniques on violent or agitated human patients. Lobotomies involved inserting an instrument into the brain through the patient’s eye socket or through holes drilled in the side of the head. The objective was to sever connections between the frontal lobes and inner brain structures such as the thalamus, known to be involved in emotion. Although some lobotomies produced highly successful results and Moniz received the 1949 Nobel Prize for his work, significant side effects such as extreme lethargy or childlike impulsiveness detracted from these benefits. Lobotomy was used widely for years, leaving many people devastated by these permanent side effects, and because of this there is an ongoing movement challenging the awarding of the Nobel Prize to Moniz. The development of antipsychotic drugs in the 1950s provided a safer way to treat violent individuals and brought the practice of lobotomy to an end (Swayze, 1995).

Psychosurgery is rarely used these days and is reserved only for extremely severe cases for which no other interventions have been effective and the symptoms of the disorder are intolerable to the patient. For instance, psychosurgery is sometimes used in severe cases of OCD in which the person is completely unable to function in their daily life and psychological treatment and medication are not effective. In contrast to the earlier days of lobotomy in which broad regions of brain tissue were destroyed, modern psychosurgery involves a very precise destruction of brain tissue in order to disrupt the brain circuits known to be involved in the generation of obsessions and compulsions. This increased precision has produced better results. For example, people suffering from OCD who fail to respond to treatment (including several trials of medications and cognitive behavioural treatment) may benefit from specific surgical procedures called cingulotomy and anterior capsulotomy. Cingulotomy involves destroying part of the corpus callosum (see Figure 3.18) and cingulate gyrus (the ridge just above the corpus collosum). Anterior capsulotomy involves creating small lesions to disrupt the pathway between the caudate nucleus and putamen. Because of the relatively small number of cases of psychosurgery, there are not as many studies of these techniques as there are for other treatments; however, available studies have shown that psychosurgery typically leads to substantial improvements in both the short and long term for people with severe OCD (Csigó et al., 2010; van Vliet et al., 2013).

656

A final approach, called deep brain stimulation (DBS), combines the use of psychosurgery with the use of electrical currents (as in ECT and TMS). In DBS, a treatment pioneered only recently, a small, battery-powered device is implanted in the body to deliver electrical stimulation to specific areas of the brain known to be involved in the disorder being targeted. This technique has been successful for OCD treatment (Abelson et al., 2009) and can provide benefits for people with a variety of neurologic conditions. The tremor that accompanies Parkinson’s disease has proven to be treatable in this way (Perlmutter & Mink, 2006), as have some cases of severe depression that are otherwise untreatable (Mayberg et al., 2005). The early view of psychosurgery as a treatment of last resort is being replaced by a cautious hope that newer, focused treatments that target brain circuits known to be functioning abnormally in those with certain mental disorders can have beneficial effects (Ressler & Mayberg, 2007).