Biomedical approaches to treatment

There are three very similar learning outcomes in the IB psychology curriculum that can really be taught as one.  The first learning outcome is Examine biomedical, individual and group approaches to treatment. The second learning is exactly the same, except that it says "to the treatment of one disorder."  It makes sense to focus on the second learning outcome since it asks you to focus on a single disorder. The exam cannot specify which disorder, but it should be either an affective, anxiety or eating disorder, depending on which you have studied. 

The third learning outcome asks you to discuss the relationship between etiology and therapeutic approach in relation to one disorder.  This asks you to look at why we think that the therapy may work and what assumptions are made about the disorder when adopting different approaches to therapy.  This third question is not restricted to a single level of analysis, so when looking at this question it is important to consider more than one level of analysis, or even the benefit of an eclectic approach to treatment.

Neurotransmission

Before we begin looking at the role that drug therapy plays in a disorder like depression, it is important that we first revise the mechanisms of neurotransmission. One of the theories about the origins of depression has to do with the levels of serotonin and norepinephrine in the synapses.  Many drugs have focused on the Serotonin hypothesis.  As you may remember, there is a correlation between low levels of serotonin and depression.  It is not clear whether this is the cause of depression, or if this is the cause of some of the symptoms of depression. If you have forgotten what this means, go to the class notes on the biological origins of depression.

There are three ways that the process of neurotransmission can be stopped. First, the receptor site of the post-synaptic cleft can be blocked.  This is how some anxiolytic drugs work to treat anxiety disorders.  They block the receptor sites of norephinephrine and thus the neurotransmitter cannot do its job.  This is not one of the ways that depression is currently treated.

A neurotransmitter is also sometimes broken down in the synapse by enzymes. This was the case with acetylcholinesterase, which breaks down acetylcholine in the synapse. You may remember that from the study by Martinez & Kesner. Physostigmine broke down this enzyme and therefore more acetylcholine was available in the synapse, making memory consolidation more efficient in rats. In the treatment of depression, monoamine oxidase (MAO) breaks down serotonin.  We will see that MAO inhibitors work by breaking down the enzyme and thus leaving more serotonin in the synaptic cleft.

Finally, neurotransmission is affected by reuptake pumps.  After the neurotransmitter is released and quickly binds to the post-synaptic cleft, the neurotransmitter is reabsorbed into the terminal buttons.  This has to do with the action potential of the neuron.  You do not need to understand why reuptake happens, but you should understand what it is and why it is important.  Prozac blocks this process of reuptake and thus allows there to be higher levels of serotonin in the synapse. Below is a video that demonstrates how Prozac works with regard to neurotransmission.

Drug treatments for depression

There are three drug treatments that are commonly used with depressed patients: tricyclic drugs such as Imipramine (sold as Tofranil), Selective Serotonin Reuptake Inhibitors (SSRIs) such as Prozac and MAO inhibitors such as Parnate.  Although early indication were that the SSRIs were clinically more effective than either tricyclics or MAO inhibitors, it now appears that the clinical effectiveness of al three classes of drugs is about the same. The SSRIs, however, have the fewest side effects and therefore are most often prescribed.

Tricyclics

Tricyclic drugs were among the first drug treatments for depression in the 1950s. They increase the levels of both norepinephrine (noradrenaline) and serotonin by interfering with the reuptake of the neurotransmitters. They have a delayed effect, but between 50 - 70% of patients will show improvement within two to three weeks of starting treatment.  When looking at the effectiveness of this drug, read the studies below.  Placebo testing has found that 30% of those that receive a placebo also show improvement.

Tricyclic drugs have many side effects.  These include dry mouth, cardiovascular problems, weight gain, constipation, blurred eyesight, sexual dysfunction, and disorientation. Tricyclics may also be used for suicidal overdoses. As you can see, some of the side effects of the drugs are rather serious. You should note that it is a small number of patients who experience these side effects.  Because we know the side effects, some patients are not given the drugs. For example, those with a history of cardiovascular problems are not given the drugs, as they are the ones most likely to experience serious side effects.

SSRIs

SSRIs are described as "selective" because they affect only the reuptake pumps responsible for serotonin, as opposed to earlier antidepressants, which affect other neurotransmitters as well, and as a result, SSRIs have fewer side effects.  SSRIs are less toxic than other antidepressants and thus overdose is not as common.

MAO inhibitors

MAO inhibitors increase the availability of serotonin by inhibiting the action of monoamine oxidase, an enzyme that normally breaks down neurotransmitters in the synaptic cleft. This drug is often used for what is called "atypical depression."  MAO inhibitors are problematic in that they have strong contraindications - that is, foods that should not be taken when using the medicine. When taking MAO inhibitors, foods high in thyamine should be taken.  These include aged cheeses, red wines and some vegetables like fava beans and asparagus. Some research, however, has indicated that this is not well supported.

Evaluation of biomedical approaches

Strengths

  • For patients suffering from severe depression, the use of biological treatments can provide relief from symptoms which would then allow for psychological treatments to be possible.
  • Drug treatments have allowed for out-patient care and has allowed for a decrease in institutionalization.

Limitations

  • How these drugs alleviate depression is unknown.  Even though they boost levels of neurotransmitters in the brain within days or even hours of use, it usually takes several weeks of treatment before a therapeutic benefit results. And not all patients respond to them.  Remember, the serotonin hypothesis has been highly criticized as an etiology to explain the origins of depression.
  • Side effects are a serious concern. 
  • High relapse rates. Psychological therapies tend to have a better long-term prognosis. Neale et al (2011) conducted a meta-analysis of studies on relapse rates and found that patients who receive only psychological treatment have a 25% risk of relapse, compare to a 42% risk of relapse if they only were on medication. Pampallona (2004) carried out a meta-analysis and found that a combination of drug and psychological treatments resulted in significant improvement compared to either treatment alone.
  • Drug therapies treat symptoms but they may not get to the root of the problem. They may neglect important psychological or social factors by taking a reductionist approach rather than a holistic approach to the disorder. Don’t dismiss the fact that drugs treat symptoms, as the symptoms can be quite devastating.
  • Anti-depressants and anti-anxiety drugs may lead to discontinuation syndrome.  This is the phrase used by the pharmaceutical companies for withdrawal symptoms from prescribed drugs.

Effectiveness studies

The effectiveness of drug treatment is best tested by longitudinal studies with placebo control groups and double blind assessment. But effectiveness is difficult to evaluate for several reasons:

  • Not all depression is the same.  The extent of the depression may be from mild to severe. Different types of depression may also have different causes.
  • Their may be a misdiagnosis.
  • There are complicating factors such as other mental health issues (comorbidity), physical issues or environmental factors - for example, domestic violence, stressful work environments, financial issues.
  • Since most care is out-patient care, it is not really possible to know if the patient is appropriately and consistently taking the medication.
  • Many patients also receive psychotherapy, making it difficult to isolate variables.

Many psychologists argue that outcome based studies - that is, studies which test for effectiveness of the drug by seeing how many patients are eventually symptom free -  are inappropriate and that process based research is better suited to studying the effects of treatment. Process based research looks at changes in the behaviour of the patient over time, recognizing that there are many variables that may affect the mental health of a patient.

There are, however, several studies that show that point to a limited effect of drug treatment.

  • Kirsch & Sapirstein (1998) carried out a meta-analysis of 19 studies with over 2300 patients. Found that drugs were only 25% more effective than placebos.
  • Blumenthal found that exercise was just as effective as SSRIs in treating depression in the elderly.
  • Elkin et al (1989) found that there was no difference in the effectiveness of CBT and drug treatment. 50% improved, while 29% improved with only a placebo.
  • A 2010 comprehensive review conducted by NICE concluded that antidepressants have no advantage over placebo in the treatment of short term mild depression, but there is evidence that they may be successful in the treatment of chronic mild depression.

A study in The New England Journal of Medicine argues that one of the problems of studies of effectiveness of anti-depressants is publication bias.  As a result, the published studies exaggerate the effectiveness of SSRIs like Prozac. 94% of studies actually published were positive outcomes; when published and unpublished studies were included for analysis, the percentage of positive outcomes was 51%.

Checking for understanding

1.  What are the three ways that drugs may work to regulate neurotransmission?

Drugs may block the receptor site on the post-synaptic cleft; they may inhibit the reuptake of neurotransmitters into the terminal buttons of the axons; they may break down enzymes which have the role of breaking down neurotransmitters in the synapse.

2. Why are SSRIs the preferred drug treatment today?

SSRIs are the preferred drug simply because they have fewer side effects.  This does not mean that they have no side effects, but that the rate of side effects is much lower.  In addition, the toxicity of the drug is lower than tricyclic. This means that it is difficult to overdose on the drug.  Since suicidal ideation is part of depression, this is an important consideration.

3. Why is it an important strength of drug therapy that out-patient care has become the norm in the treatment of depressed patients?

Before there was out-patient care, many patients were hospitalized.  The results of hospitalization include separation from those you love that may support you in your depression.  It has been found that institutionalization can lead to negative behaviours that can compound the problems of depression.

4. What does research say about relapse rates with drug treatments?

Research indicates that patients who are treated only by drug therapy tend to have a high relapse rate.  This is because though their symptoms may have been treated, they have not learned psychological coping strategies for dealing with their feelings of depression.  The best approach appears to be a combination of drug therapy (to alleviate symptoms) and psychological therapy.

5. What is a double blind study? How would it be applied to a study of a drug's effectiveness?

In a double blind study, the people carrying out the research do not know which group is getting the placebo and which group is getting the drug treatment.  In addition, when the researcher overseeing the study gets the data, she would not know which condition the individual was in. This is important because it lowers researcher bias.  If I am evaluating a person's mental health to determine whether he/she has improved, not knowing whether the person was on the placebo or on the drug will help to keep the assessment more objective.

6. Why are studies of the effectiveness of treatments problematic?

There are several reasons.  First, it is difficult to establish when a person is "over" his/her depression.  So, to simply look at an outcome rather than improvement over time (process based study) means that we may be underestimating the effects of drug treatment.  Second, many patients do not take their drugs regularly or do not follow the directions.  Also, there is the problem that when we are talking about "depression", we are talking about a range of symptoms which may be to a different extent in different patients. Finally, there is the problem that there are other variables in a patient's life that may affect their mental health.  These environmental variables may play a significant role on whether the patient improves or not.

7. What is meant by publication bias?  How does it affect research on the effectiveness of drug treatment?

Publication bias is when published research tends to favour only positive results.  Negative results - that is, when the null hypothesis is retained - is not considered very interesting and therefore is often not published.  However, when carrying out a meta-analysis of research, this means that it skews the review of literature to be more positive than it actually is.  In the case of drug treatment, in the case of the New England Journal of Medicine study, 94% of studies published were positive; when adding in those that were submitted which retained the null hypothesis but were rejected for publication, the number of studies showing positive outcomes for SSRIs dropped to around 50%.

8. With regard to drug treatment why is it important to understand the relationship between etiology and the therapeutic approach? (the third of the three learning outcomes for this lesson)

When addressing this question it is important to understand the Serotonin hypothesis.  But modern thinking about this hypothesis is that a decrease in serotonin is the result of high levels of cortisol.  If this is true, it would explain why relapses happen when only drug therapy is used as a treatment.  It also means that low levels of serotonin are one of the symptoms correlated with depression and this may explain why some people do not respond to the drug.  But the fact that there is a correlation and the correlation may be relevant to some of the symptoms of feeling down, means that addressing the neurotransmission of serotonin is perhaps a logical treatment in some cases.

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