How does psychotherapy work if depression is due to a chemical imbalance?

Anthony's comment:

Psychotherapy is a broad area of treatment with different modalities available. My experience with psychotherapy is that is gives you the insight to allow yourself to make better choices. It is my opinion that psychotherapy has been a necessary part of my treatment, as it has made me able to look inward to figure out why I engage in certain behaviors. Once you have some degree of insight you can ease your situation by avoiding certain behaviors. Psychotherapy was of use to me as a long-term treatment over a few years. Although I no longer continue with regular sessions, I still choose to have periodic contact via phone or face-to-face sessions.

Every thought, feeling, and behavior is associated with a chemical change in the brain. If thoughts, feelings, and behaviors occur with a repeated pattern, structural changes can occur in the brain as well. Learning and

Success in therapy depends on how one feels about the therapy sessions as well as the motivation from the therapist to "do the work" outside of therapy to make the changes needed.

memory involve complex chemical changes that lead to permanent structural changes in brain anatomy. For example, consider the first time that one learns how to drive a car. It requires conscious processing of complex pieces of information and integrating the information into an organized behavioral pattern. The powers of concentration at that time could be exhausting. However, with practice the skill becomes second nature as the brain adapts the skill so that much of it occurs unconsciously. Over-learned behavior such as that ultimately leads to structural and biochemical changes in the brain.

The chemistry and structure of the brain can change via one of three methods: (1) change in the environment, (2) change in brain chemistry via chemical modification with the use of psychotropic medication, and (3) learning how to modify the environment or perception of the environment by developing new skills.

Moving, changing jobs, and getting married or divorced are examples of the first method, whereas psychopharmacology is the second. Psychotherapy uses the third method. Brain imaging studies have repeatedly demonstrated, for example, that changes occur in the same brain regions of patients with obsessive-compulsive disorder on fluoxetine as those receiving cognitive-behavioral therapy. Each of these methods has its own inherent costs and benefits, and therefore none can be considered inherently better or worse than another. The effects of all three methods are generally cumulative; thus for one to have the best chance of recovery from depression, a combination of two to three methods is generally warranted.

What are the different types of medication used to treat depression? How does my doctor choose a medicine?

Medication choices include many medications within the following classes:

• Tricyclic antidepressants (TCAs)

• Monoamine oxidase inhibitors (MAOIs)

• Selective serotonin reuptake inhibitors (SSRIs)

• Serotonin norepinephrine reuptake inhibitors

• Others

TCAs and MAOIs are the oldest antidepressants. They are effective treatments but have many problematic side effects. In addition, they can be unsafe to use in patients with certain medical conditions and in older persons. MAOIs require strict adherence to a dietary plan that is free of tyramine (Table 4). Although these medications are effective for treatment of depression, they are now typically reserved for use after a person's symptoms have not improved on one of the newer medications available. The most commonly prescribed TCAs are desipramine and nortriptyline because of their better tolerated side effect profiles. Table 5 provides a list of available TCAs and MAOIs.

Table 4. Dietary Restrictions while Taking an MAOI[1]

Matured or aged cheeses Fermented or dried meats Fava and broad bean pods Tap beers

Marmite yeast extract Sauerkraut

Soy sauce and other soy products

Smoked, pickled, or fermented fish

Improperly stored meats, fish, and dairy products

Table 5. Tricyclic Antidepressants and Monoamine Oxidase Inhibitors


clomipramine (Anafranil) amitriptyline (Elavil) doxepin (Sinequan) trimipramine (Surmontil) amoxapine (Asendin) protriptyline (Vivactil) desipramine (Norpramin) nortriptyline (Pamelor, Aventyl) imipramine (Tofranil) maprotiline (Ludiomil)


phenelzine (Nardil) tranylcypromine (Parnate)

The first SSRI to enter the market was fluoxetine (Prozac) in the late 1980s. Because of its low side-effect profile relative to the TCAs and MAOIs, fluoxetine quickly became the most popular antidepressant. Several SSRIs have come on the market since (Table 6). Because SSRIs as a group are the most commonly prescribed antidepressants, the decision as to choice of medication is often in deciding between the SSRIs available. There is no good evidence that any SSRI is better than another in the treatment of depression or any of the anxiety disorders. The choice of SSRI has more to do with side-effect profiles and potential for drug-drug interactions. Discontinuation syndromes[2] are least likely from fluoxetine and are more likely from paroxetine. Fluoxetine may be a better choice for someone who tends to miss doses of medication. On the other hand, because of its long half-life[3], adverse effects will take longer to dissipate after discontinuation of the drug. In terms of potential

Table 6. Selective Serotonin Reuptake Inhibitors

fluoxetine (Prozac)

sertraline (Zoloft)

paroxetine (Paxil)

fluvoxamine (Luvox)

Citalopram (Celexa)

escitalopram (Lexapro)

interactions with other medications, fluoxetine, paroxetine, and fluvoxamine have the highest potential for such interactions. Sertraline, citalopram, and escitalopram have a lower risk for interactions. Cost may be a factor in medication choice as well, with some SSRIs now available in generic forms.

The serotonin norepinephrine reuptake inhibitors are dual reuptake inhibitors of both norepinephrine and serotonin (and, to a lesser extent, dopamine). They have similar side-effect profiles to the SSRIs but have the advantage of working through two neurotransmitter systems (Table 7). Medications classified under "other" have various mechanisms of action (Table 8). Bupropion blocks the reuptake of dopamine and norepinephrine. Bupropion does not have significant drug-drug interactions and is not associated with sexual dysfunction. Mirtazapine causes increased levels of serotonin and norepinephrine by blocking the inhibition of their release (both serotonin and norepinephrine act to turn off their own release by interacting with receptors on the sending neuron). Trazodone and nefazodone are chemically similar (trazodone is an older antidepressant), blocking serotonin reuptake as well as blocking some types of serotonin receptors directly. Trazodone is very sedating and is mainly used for insomnia, and nefazodone is not first line because of its association with some cases of liver failure.

Table 7. Serotonin Norepinephrine Reuptake Inhibitors


Mechanism of Action

Venlafaxine (Effexor)

Serotonin and norepinephrine reuptake inhibition

Duloxetine (Cymbalta)

Serotonin and norepinephrine reuptake inhibition

Desvenlafaxine (Pristiq)

Serotonin and norepinephrine reuptake inhibition

Table 8. Antidepressants With Other Mechanisms of Action


Mechanism of Action

mirtazapine (Remeron)

Blocks the inhibition of serotonin and norepinephrine


trazodone (Desyrel)

Serotonin receptor blockade and reuptake inhibition

nefazodone (Serzone)

Serotonin receptor blockade and reuptake inhibition

bupropion (Wellbutrin)

Norepinephrine and dopamine reuptake inhibition

Typically, the first decision regarding antidepressant choice is between the newer classes. All antidepressants are effective for depression, but the choice of type will likely depend on side-effect profiles, patient characteristics, physician preference, and cost. Some insurance plans have formularies restricting use to a specific medication. In these circumstances the physician would need to explain the rationale for choosing a nonformulary medicine over a formulary one. Side-effect profiles for the different medication classes noted previously here are listed in Table 9. Appendix B lists all antidepressants with their dosing ranges and formulations.

In addition to antidepressants, many other medications are used in the treatment of depression: anticonvulsants, antipsychotics, and benzodiazepines. Typically, these medications are used to address specific comorbid conditions or symptoms that are not addressed by the anti-depressant. In cases of partial response to an antidepressant, there may be medications prescribed for augmentation, including buspirone, thyroid hormone,

Table 9. Adverse Effects of Antidepressants by Class[4]

Medication Class

Potential Adverse Effects


Nausea, diarrhea, insomnia, anxiety, nervousness, dizziness, somnolence, tremor, decreased libido, sweating, anorexia, dry mouth, headache, sexual dysfunction, serotonin syndrome


Sweating, nausea, dry mouth, constipation, decreased appetite, headache, dizziness, insomnia, fatigue, drowsiness, vomiting, nervousness, pruritus, blurred vision, rash, sexual dysfunction, hypertension, tremor, unusual bleeding, cardiac effects


Dry mouth, constipation, nausea, anorexia, weight gain, sweating, increased appetite, nervousness, decreased libido, dizziness, tremor, somnolence, blurred vision, tachycardia, urinary hesitancy, hypotension, cardiac toxicity


Dizziness, headache, drowsiness, hypotension, insomnia, agitation, dry mouth, constipation, nausea, urinary hesitancy, weight gain, edema, sexual dysfunction, increased liver enzymes, toxic food and drug interactions

Others (drugs listed separately)

bupropion (Wellbutrin)

Weight loss, dry mouth, rash, sweating, agitation, dizziness, insomnia, nausea, abdominal pain, weakness, headache, blurred vision, constipation, tremor, rapid heart rate, ringing in ears, seizures

mirtazapine (Remeron)

Somnolence, appetite increase, weight gain, dizziness, dry mouth, constipation, hypotension, abnormal dreams, flu syndrome, low blood cell counts

nefazodone (Serzone)

Somnolence, dry mouth, nausea, dizziness, insomnia, agitation, constipation, abnormal vision, confusion, liver failure

trazodone (Desyrel)

Sedation, hypotension, dizziness, blurred vision, headache, loss of appetite, sweating, restlessness, rapid heart rate, prolonged erection

or even a stimulant such as methylphenidate. Lately, some of the newer atypical antipsychotic medications have been approved and advertised for use in some types of depression, such as bipolar depression, or to augment other antidepressants to boost their effectiveness. These medications work by an entirely different mechanism from traditional antidepressants and have significant side effects associated with them, so it is critical to speak to your doctor before taking them.

  • [1] This list is intended to be a general guideline only; more specific information on restrictions as well as permissible foods should be obtained from your doctor.
  • [2] physical symptoms that occur when a drug is suddenly stopped.
  • [3] the time it takes for half of the blood concentration of a medication to be eliminated from the body. Half-life determines as well the time to equilibrium of a drug in the blood and determines the frequency of dosing to achieve that equilibrium.
  • [4] Listed adverse effects are not exhaustive of side effects as reported in the Physicians' Desk Reference. Rather more common effects within each group were included as well as some more serious effects. Side effect profiles of medications within a class may vary. Any concern about an adverse effect from a medication should be discussed with your doctor.
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