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 15.2).

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Antipsychotic drugs are medications that are used to treat schizophrenia and related psychotic disorders. The first antipsychotic drug, back in the 1950s, was chlorpromazine (brand name Thorazine), which was originally developed as a sedative. 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. 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.

Antipsychotic medications are believed to block dopamine receptors. As you read in the Psychological Disorders chapter, the effectiveness of schizophrenia medications led to the dopamine hypothesis, suggesting that schizophrenia may be caused by excess dopamine in the brain. Research has indeed found that dopamine overactivity in some areas of the brain is related to the more bizarre positive symptoms of schizophrenia, such as hallucinations and delusions (Marangell et al., 2003). Unfortunately, the negative symptoms of schizophrenia, such as emotional numbing and social withdrawal, may be related to dopamine underactivity in other areas of the brain. This may explain why antipsychotic medications do not relieve negative symptoms well.

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 (Risperdal), and olanzapine (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 block both dopamine and serotonin receptors. Serotonin has been implicated in some of the core difficulties in schizophrenia, such as cognitive and perceptual disruptions, as well as mood disturbances, which may explain why atypical antipsychotics can provide relief for both the positive and negative symptoms of schizophrenia (Bradford, Stroup, & Lieberman, 2002).

Like most medications, antipsychotic drugs have side effects. These can include motor disturbances such as 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).

Antianxiety 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 Behavior 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).

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Nonetheless, these days, doctors are relatively cautious when prescribing benzodiazepines. One concern is that these drugs can be highly addictive. They also have side effects, especially drowsiness, but also negative effects on coordination and memory. And benzodiazepines combined with alcohol can depress respiration, potentially causing accidental death.

Antidepressants are a class of drugs that help lift people’s moods. Two classes of antidepressants were introduced in the 1950s, the monoamine oxidase inhibitors (MAOIs) and the tricyclic antidepressants. MAOIs prevent the enzyme monoamine oxidase from breaking down neurotransmitters such as norepinephrine, serotonin, and dopamine. However, despite their effectiveness, MAOIs are rarely prescribed anymore due to side effects such as dizziness and loss of sexual interest, as well as potentially dangerous interactions with other common medications. Tricyclic antidepressants are still sometimes used, but they also have serious side effects, including dry mouth, constipation, difficulty urinating, blurred vision, and racing heart (Marangell et al., 2003).

Today, the most commonly used antidepressants 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 15.3).

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 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 commonly treated with mood stabilizers, which are medications used to suppress swings between mania and depression. Commonly used mood stabilizers include lithium and valproate.

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In a survey of more than 2,000 Americans, 7% of those suffering from anxiety disorders and 9% of those suffering from severe depression reported using alternative “medications” such as herbal medicines, megavitamins, homeopathic remedies, or naturopathic remedies to treat these problems (Kessler et al., 2001). 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 isn’t simple. Herbal products are not considered medications by regulatory agencies like the U.S. Food and Drug Administration, 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).

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There is research support for the effectiveness of some herbal and natural products, but the evidence is not overwhelming (Lake, 2009). For example, some studies have shown that St. John’s wort (a wort, it turns out, is an herb) has an advantage over a placebo condition for the treatment of depression (e.g., Lecrubier et al., 2002), whereas other studies 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 a placebo at decreasing depression (see FIGURE 15.4) (Lewis et al., 2011; Parker 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.

Given that psychological treatments and medications both have 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? The answer often depends 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. But in the case of mood and anxiety disorders, medication and psychological treatments are equally effective. One study compared cognitive behavior therapy, imipramine (an antidepressant), 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. But the combination of CBT plus imipramine 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 15.5). More is not always better.

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 neighboring cortical areas during neighboring cortical areas during this challenge (see FIGURE 15.6). 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.

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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 cannot prescribe 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 (Fox et al., 2009). Only Illinois, Louisiana, and New Mexico currently allow licensed and specially trained psychologists prescription privileges, but other states are considering it (Munsey, 2008). Opponents argue that psychologists do not have the medical training to understand how medications interact with other drugs. Proponents argue that patient safety would not be compromised as long as rigorous training procedures were established. 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 doesn’t 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.

Electroconvulsive therapy (ECT), sometimes referred to as shock therapy, 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 anesthesia 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, placebos, and antidepressant drugs such as tricyclic antidepressants and MAOIs (Pagnin et al., 2008).

Transcranial magnetic stimulation (TMS) is a treatment that involves placing a powerful pulsed magnet over a person’s scalp, which alters neuronal activity in the brain (see the Neuroscience and Behavior chapter). Unlike ECT, TMS is noninvasive, and side effects are minimal: They include mild headaches 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).

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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 from seasonal affective disorder (SAD; see the Psychological Disorders chapter). 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 behavior, 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).

Today, psychosurgery is reserved only for extremely severe cases for which both no other interventions have been effective and the symptoms of the disorder are intolerable to the patient. 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 symptoms. For example, people suffering from OCD who fail to respond to treatment (including several trials of medications and cognitive behavioral treatment) may benefit from specific surgical procedures to destroy part of the corpus callosum (see FIGURE 3.16) and cingulate gyrus (the ridge just above the corpus collosum), two brain areas known to be involved in the generation of obsessions and compulsions. 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).

A final approach, called deep brain stimulation (DBS), combines the use of psychosurgery with the use of electric 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).

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