Chapter 16 Psychology

Jaime Stevens, MD, MPH, Thomas A. Brown, MD, Sonali J. Shah

Insider’s Guide to Psychology for the USMLE Step 1

Psychology is a straightforward subject on the USMLE if studied for correctly. Focus on learning the diagnostic criteria for the diseases covered in First Aid. Popularly tested subjects include personality disorders, defense mechanisms, delirium versus dementia, eating disorders, panic disorder, drug abuse and withdrawal, and depression. Take time to learn the antipsychotic drugs and their side effects. They are commonly tested on Step 1.

Case 16-1

A 20-year-old college student has been doing poorly for the past 8 months. He has become socially withdrawn and apathetic, and his grades, previously good, have been suffering. He complains to the campus physician that he has been hearing voices and that the TV news anchor has been giving him secret messages telling him to infiltrate the Russian KGB and thwart their assassination attempt of the President. He also wants to go into hiding because he believes that the CIA is after him. An extensive workup to identify organic causes of his symptoms (thyroid function tests, drug screening, head computed tomography [CT], and magnetic resonance imaging [MRI]) is negative.

1 What is the most likely diagnosis?

Schizophrenia, a thought disorder that occurs in approximately 1% of the population, is most likely. However, the differential diagnosis includes schizoaffective disorder, mood disorder with psychotic features, and psychosis secondary to a general medical condition or substance abuse.

Note: The typical age at onset of schizophrenia is 18 to 24 years in men and 26 to 45 years in women.

2 According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), what criteria must be met in order to make the diagnosis of schizophrenia?

Two or more of the following active-phase symptoms must be present for a 1-month period (or less if successfully treated):

1. Delusions (substantially irrational beliefs, e.g., a belief that you’re the reincarnation of Fred Astaire)

2. Hallucinations (e.g., hearing voices that only you can hear) (Note: The primary cause of auditory hallucinations in a psychotic patient is schizophrenia. You should make this association for the USMLE.)

3. Disorganized speech (e.g., incoherence)

4. Grossly disorganized or catatonic behavior

5. Negative symptoms (e.g., social withdrawal)

In addition, the preceding symptoms must cause negative effects on major areas of functioning such as work, interpersonal relations, or self-care. The duration of the disturbance must persist for at least 6 months, including at least 1 month of active-phase symptoms listed here.

3 What is the diagnosis if this man had suffered these symptoms for only the past 3 months rather than for 8 months (with a negative workup for other causes)?

Schizophreniform disorder, which is diagnosed in a patient displaying symptoms of schizophrenia for a period of more than 1 month and no longer than 6 months in duration.

Step 1 Secret

Many psychological disorders are associated with time intervals that are required to make a definitive diagnosis of the disease. The USMLE will expect you to know these time intervals (e.g., schizophreniform disorder and schizophrenia both present with the same symptoms, but schizophrenia is diagnosed only in patients who are symptomatic for at least 6 months).

4 What is the likely diagnosis if this man presented with these symptoms and later developed depressive, manic, or mixed features?

Schizoaffective disorder is more likely because the “affect” is involved. There is also the usual laundry list of DSM-IV criteria to make this diagnosis, but you will not be required to know this for the Step 1 examination. Schizoaffective disorder differs from major depression with psychotic features in that the latter does not involve delusions and hallucinations in the absence of significant mood symptoms for more than 2 weeks (i.e., if longer than 2 weeks, it is schizoaffective disorder).

Step 1 Secret

You are responsible for learning about schizoaffective disorder for Step 1, but because it is such a nit-picky diagnosis to make, you are far more likely to be tested on schizophrenia and schizophreniform disorder than on schizoaffective disorder.

5 What would your diagnosis be if this man had symptoms of schizophrenia following a severe stressor and these symptoms resolved within 2 weeks?

He would be suffering from a brief psychotic disorder; in this case, it would be a reactive psychosis, as it is associated with marked stressors. A brief psychotic disorder is a disorder that lasts a short period of time, less than a month, but at least 1 day. It cannot be due to a general medical condition, associated with a mood disorder, or caused by substance use. This disorder does not require that severe stressors be present. In women, it additionally may have postpartum onset (if within 4 weeks of delivery), in which case it would be called postpartum psychosis. If this had followed or had been attributed to a medical illness, it would be diagnosed as psychosis secondary to a general medical condition.

6 What are the four primary types of schizophrenia?

Catatonic schizophrenia is characterized by two or more of the following: cataplexy (define) or stupor, excessive motor activity, resistance to instructions or attempts of movement, peculiar movements or posturing and mannerisms or grimacing, and echolalia or echopraxia (mimicking of others’ speech or movements).

Disorganized schizophrenia includes disorganized speech and behavior and flat or inappropriate affect and does not meet criteria for catatonic schizophrenia.

Paranoid schizophrenia is characterized by delusions of persecution and absence of disorganized speech, catatonic behavior, and flat or inappropriate affect. This patient’s symptoms are most consistent with paranoid schizophrenia.

Residual schizophrenia is characterized by absence of prominent delusions, hallucinations, or catatonia, and there is continuing evidence of the disease such as negative symptoms and odd beliefs.

Step 1 Secret

It is not hugely important to know the different types of schizophrenia for the USMLE. Read this section through once or twice, but do not worry about committing these facts to memory.

7 What neurotransmitter abnormality is thought to play the primary role in this man’s disorder?

The current theory is that excess dopamine activity in certain regions of the brain is the cause of schizophrenia. There are several pieces of evidence in support of this theory. Some researchers have shown that positron emission tomography (PET) scans of schizophrenic patients’ basal ganglia show an increased number of D₂ receptors when compared with unaffected control subjects. Patients with schizophrenia who are treated with dopamine receptor antagonists show a beneficial response. Additionally, drugs with dopaminergic effects will aggravate existing psychosis and, in some patients, can result in new-onset psychosis (see question 8).

8 What are the differences between the positive and negative symptoms experienced by schizophrenics?

Positive symptoms are symptoms whose presence is abnormal. They include thought disturbances, delusions, and auditory and visual hallucinations. These symptoms are mediated by increased levels of dopamine in the mesolimbic pathway and can be treated with typical antipsychotic drugs. Negative symptoms are those that indicate an absence of a habit, expression, or quality present in a majority of the general population. They can include social withdrawal and isolation, anhedonia, and apathy. Negative symptoms are the result of decreased activity of mesocortical dopaminergic projections. They can be exacerbated by use of typical antipsychotics.

9 What is the relationship between schizophrenia and suicide?

Unfortunately, people with schizophrenia are at greatly increased risk for attempting suicide, and between 10% and 15% of schizophrenics do successfully commit suicide.

10 When initiating therapy for patients like this college student, it is important to keep potential side effects in mind and to educate the patient about them. What type of side effects are more commonly seen with high-potency antipsychotics such as haloperidol and fluphenazine than with other antipsychotics?

Extrapyramidal side effects (EPS) such as acute dystonia, parkinsonism, akathesia, and tardive dyskinesia (TD) are more commonly seen. Acute dystonia results in excessive muscle tone and muscle spasms (e.g., torticollis, laryngospasm) after only short-term exposure (typically within 3-5 days) to antipsychotics. Parkinsonism is characterized by shuffling gait, cogwheel rigidity, bradykinesia, and resting tremor. Onset is usually not until after a couple of weeks of therapy. Akasthesia is a subjective sensation of inner restlessness or desire to move. Individuals with this condition may appear anxious or agitated and may move about and pace, as they are unable to sit still. TD presents with involuntary movements of the tongue, lips, face, trunk, and extremities (generally irreversible) and occurs in patients treated with long-term dopaminergic antagonist medications (months to years) of high-dose antipsychotics. The risk of developing TDs is about 3% per year with typical agents.

11 What is the correct treatment for the previously mentioned extrapyramidal side effects?

Both dystonia and drug-induced parkinsonian syndrome are best treated with an anticholinergic such as benztropine (note that this would be a good opportunity to review the role of acetylcholine in the basal ganglia pathways). In addition, if there is acute airway obstruction due to laryngeal spasms in acute dystonia, intravenous diphenhydramine should be used urgently. Akathesia frequently does not improve with anticholinergics; administration of a beta blocker is often the first step. Lowering the dose or switching medication may be necessary. If TDs appear, the offending drug should be discontinued immediately (hence the importance of the education). Unfortunately, TDs often do not improve or resolve despite discontinuation of the drug. All antipsychotics, with the exception of clozapine, may produce TD, but it is most commonly seen with the typical agents prescribed. The patient should therefore be switched to an atypical agent or to clozapine. Anticholinergics have no benefit in these patients and may actually worsen symptoms.

12 How might this man develop the following symptoms if he is being treated with low-potency typical antipsychotics such as chlorpromazine or thioridazine?

A. Urinary retention

The term low-potency typical antipsychotics refers to the fact that a greater dose is required to reach the same dopaminergic effect. The low-potency antipsychotics, in addition to blocking D₂ receptors, also block histaminic, α-adrenergic, and muscarinic receptors (i.e., the HAM receptors) to a much greater extent than the high-potency typical antipsychotics. Blockade of the muscarinic cholinergic receptors on the detrusor muscle of the bladder results in urinary retention.

Note: The muscarinic antagonism also causes the common anticholinergic side effects of dry mouth, loss of visual accommodation, and constipation.

B. Orthostatic hypotension

Orthostatic hypotension can be caused by α-blockade. As a result, higher doses are used, leading to increased antagonism of the α-receptor.

C. Sedation

H₁ blockade can produce a sedative effect. Administration of the drug at bedtime may reduce daytime sedation.

13 Perhaps the most feared complication of antipsychotics is an idiosyncratic reaction characterized by severe muscle rigidity, myoglobinuria and elevated plasma creatine kinase, fever, autonomic instability, and altered mental status. What is the name of this lethal side effect and what is the treatment?

Neuroleptic malignant syndrome (NMS) may occur with any antipsychotic, aside from clozapine, but more commonly is seen with the typical agents; the offending drug should be stopped immediately. In addition, NMS can be treated with dantrolene or dopamine agonists such as bromocriptine.

Step 1 Secret

Neuroleptic malignant syndrome (NMS) and side effects of high-potency and low-potency neuroleptics are frequently tested on Step 1. Be sure to know which drugs fall into which of these two categories.

14 How do typical and atypical antipsychotics differ with respect to their mode of action and to their effect on positive and negative symptoms?

Atypical antipsychotics (e.g., clozapine) are “atypical” in that they are more effective against the negative symptoms of schizophrenia and are much less likely to cause extrapyramidal side effects (e.g., acute dystonia, TD) than are the typical antipsychotics. In addition to dopamine receptor blockade, atypicals block the serotonin receptor of the 5-HT₂ subtype; this is thought to offer some protection against EPS. The thought is that atypicals are effective in mesolimbic blockade of dopamine (hyperactive in schizophrenics) without significant blockade of the mesocortical circuit (hypoactive in schizophrenics). In addition, the atypicals have other dopamine receptor actions. For example, clozapine is a very effective D₄ antagonist, and aripiprazole is a dopamine autoreceptor agonist and a D₂ partial agonist.

15 Which one of the four major dopamine pathways of the brain is responsible for the following symptoms in schizophrenia?

A. Gynecomastia, galactorrhea, and menstrual dysfunction with antipsychotic use

The tuberoinfundibular pathway involves projection of dopamine neurons in the arcuate nucleus to the median eminence (below the hypothalamus). Dopamine released at this site normally inhibits the secretion of prolactin from the anterior pituitary gland. Some antipsychotic drugs block dopamine in the tuberoinfundibular pathway, causing hyperprolactinemia. This may cause gynecomastia, galactorrhea, and menstrual dysfunction secondary to prolactin-mediated inhibition of gonadotropin-releasing hormone (GnRH).

B. Positive symptoms

The mesolimbic pathway involves projection of dopamine neurons in the ventral tegmentum to the nucleus accumbens. Hyperactivity of this pathway is thought to be responsible for the positive symptoms such as hallucinations, delusions, and agitation.

C. Negative symptoms

The mesocortical pathway involves projection of dopamine neurons in the ventral tegmentum to the frontal lobes. The idea is that hypoactivity of this pathway in schizophrenics may be responsible for the negative symptoms of social withdrawal and flat affect.

D. Parkinsonism with antipsychotic use

The nigrostriatal pathway is a neural pathway that connects the substantia nigra with the striatum. Loss of neurons in this pathway is responsible for Parkinson’s disease, so it is no wonder that blockade of dopamine will cause parkinsonism (bradykinesia, rigidity, masked facies, resting tremor, shuffling gait). Fortunately, these symptoms are reversible with discontinuation of the antipsychotics.

Step 1 Secret

You should know the functions of each of the dopaminergic pathways and the symptoms involved with dysregulation of these pathways.

16 Recent studies have suggested that there is no large difference in effectiveness and tolerability between the typical and atypical drugs, with the exception of clozapine. Although the typicals have significant side effects, the atypicals also come with their fair share of problems. Which atypicals are most strongly correlated with the following side effects?

A. Gynecomastia, galactorrhea, and menstrual dysfunction

Risperidone is similar to typical antipsychotics in that it is a very potent blocker of the D₂ receptor. D₂ receptor blockade of the tuberoinfundibular pathway leads to hyperprolactinemia, which causes gynecomastia, galactorrhea, and menstrual dysfunction.

B. Hyperlipidemia and diabetes

Olanzapine and clozapine appear to carry the greatest risk, followed by risperidone and quetiapine. However, in 2003 the U.S. Food and Drug Administration (FDA) requested manufacturers of all atypical antipsychotics to include product label warnings about the potential for an increased risk of hyperglycemia and diabetes.

C. Increasing the QT interval

Of the atypical drugs, ziprasidone has the greatest effect on QT prolongation and should therefore be avoided in patients with increased QT intervals or known heart disease.

D. Increased mortality risk with treatment of dementia-related psychosis in the elderly

A placebo-controlled trial in which risperidone and olanzapine were studied found that for the treatment of dementia-related psychosis in the elderly, there was an associated higher death rate versus placebo. In April 2005, the FDA therefore required manufacturers of all atypical antipsychotics to include a boxed warning in their labeling noting this risk.

17 Why is clozapine recommended for use only in schizophrenics whose symptoms are refractory to treatment with other antipsychotics?

Clozapine is an atypical antipsychotic that often works in patients who have been refractory to other antipsychotics. The big drawback of using clozapine is that it can precipitate a fatal agranulocytosis (1% per year) and therefore necessitates weekly monitoring of blood levels for the first 6 months of therapy before the dose is reduced to a somewhat longer interval. Other drugs that can cause agranulocytosis include carbamazepine, colchicine, propylthiouracil, methimazole, and dapsone. The USMLE loves to ask questions on this concept!

Summary Box: Psychotic Disorders

Schizophrenia is defined as presence of two symptoms for 1 month (delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, negative symptoms) AND signs of illness for at least 6 months.

Schizoaffective disorder meets criteria for schizophrenia and criteria for major depression, mixed disorder, or manic episode. It is accompanied by delusions and hallucinations for 2 weeks without mood symptoms.

Schizophreniform disorder meets criteria for schizophrenia, but duration is 1 to 6 months.

Brief psychotic disorder is described as presence of schizophrenic symptoms lasting 1 day to 1 month.

Delusional disorder consists of presence of nonbizarre delusions for at least 1 month AND no other symptoms of schizophrenia.

Atypical antipsychotics are more effective against the negative symptoms of schizophrenia and are much less likely to cause extrapyramidal side effects.

Low-potency typical agents have high incidence of anticholinergic side effects, sedation, and orthostatic hypotension.

High-potency typical agents have high incidence of extrapyramidal side effects.

There is no large difference in effectiveness and tolerability between the typical and atypical antipsychotics, with the exception of clozapine.

Case 16-2

A 22-year-old college man nicknamed “Roller-coaster” by his friends complains of problems with his mood and is referred to a psychiatrist by the campus physician for further evaluation. He states that for the past week he has been incredibly productive because he has required very little sleep. During the interview, the physician notes pressured speech, distractibility, euphoric mood, and psychomotor hyperactivity. The patient denies any history of auditory or visual hallucinations or use of alcohol or other drugs. Just prior to this period, however, he experienced a 2-month period characterized by hypersomnia, anhedonia, decreased appetite, and psychomotor retardation. Physical examination is noncontributory, and laboratory tests indicate normal thyroid activity.

1 What is the diagnosis?

He has bipolar disorder—specifically, bipolar I.

Note: Bipolar I is characterized by manic episodes lasting at least 1 week, whereas the milder bipolar II requires only a hypomanic episode lasting at least 4 days for diagnosis. The major difference from a manic episode is the lack of social or occupational dysfunction.

Manic episodes consist of abnormal mood with three or more of the following symptoms present for at least 1 week:

Befuddled/distracted

Ideas upon ideas (racing thoughts)

Grandiosity

Sleep decrease

Hypersexuality

Irresponsible actions

Focused activity

Talkative

Step 1 Secret

You can easily recall the symptoms of manic episodes by remembering that manic episodes cause a BIG SHIFT in mood.

2 Was the previous depressive episode required to make the diagnosis of bipolar in “Roller-coaster”?

No, only a single manic episode is required. All patients who have experienced a manic episode are considered bipolar, regardless of whether they have additionally suffered a depressive episode or not. This can be confusing, as the term “bipolar” implies manic and depressive features. However, most patients with a history of manic episodes will ultimately develop a depressive disorder as well.

Note: Unlike bipolar I, bipolar II does require at least one major depressive episode. There is also cyclothymia, which requires a period of at least 2 years during which there have been both periods of hypomania and depression, but the depressive episodes do not fulfill requirements for major depression and the patient has not been symptom-free for more than 2 months.

3 The physician prescribes lithium and informs “Roller-coaster” that he needs to have his blood levels of lithium monitored regularly. Why is this necessary?

There is only a small difference between the therapeutic and toxic concentrations of lithium (i.e., its therapeutic index is low, which makes it a dangerous drug). Lithium toxicity presents with coarse tremor (fine tremor is a common side effect of lithium), stupor, ataxia, vomiting, diarrhea, and cardiac arrhythmias.

4 After taking lithium for an extended period of time, “Roller-coaster” develops polyuria and polydipsia. The urine has a low osmolarity, and administration of antidiuretic hormone (vasopressin) does not have a significant effect on either the polyuria or the low urine osmolarity. What is happening?

A distinctive but rare side effect of lithium is nephrogenic diabetes insipidus. This occurs when the kidneys do not respond effectively to antidiuretic hormone (ADH) and so do not conserve water or concentrate the urine effectively—hence the polyuria and polydipsia.

5 True or false: Treatment of this lithium-induced nephrogenic diabetes insipidus with loop diuretics may be effective in decreasing his symptoms of polyuria

True. Although this effect is seemingly counterintuitive, loop diuretics and thiazide diuretics will actually decrease polyuria in nephrogenic diabetes insipidus because they promote proximal tubular reabsorption. However, extracellular fluid depletion can also increase the risk of lithium intoxication by enhancing lithium reabsorption at the proximal tubule, so careful monitoring is required to avoid lithium toxicity. Amiloride is perhaps the best choice of a diuretic because it is least likely to increase lithium levels.

6 “Roller-coaster” also mentions that he has become rather depressed after being on the lithium for a while, is having memory problems, and seems to be cold all the time. Rather than just putting this patient on an antidepressant, the physician orders thyroid-stimulating hormone (TSH) and T₄ (thyroxine) levels first. Why?

Another side effect of lithium is hypothyroidism, which can cause the previously mentioned symptoms.

Note: Although the issue is not pertinent to this patient, lithium can also lead to pregnancy problems. A well-established complication of lithium is Ebstein anomaly, which is a congenital malformation of the heart characterized by apical displacement of the tricuspid valve leaflets.

7 Because “Roller-coaster” is not tolerating lithium well, his physician decides to substitute a drug that is effective not only for bipolar disorder but also for several seizure disorders. What is this drug and what regular monitoring should be done?

Because valproic acid has lower toxicity and fewer side effects than lithium, this drug has actually become the mood stabilizer of choice. Valproic acid is also effective for absence seizures, partial seizures, and generalized seizures. It is worth mentioning that valproic acid is also more effective than lithium in rapid-cycling and mixed-state episode bipolar disorder. Very rare but potentially fatal side effects of valproic acid therapy include necrotizing hepatitis (children are at increased risk) and agranulocytosis. Periodic monitoring of liver enzymes and blood cells is therefore indicated in patients on long-term valproic acid therapy. Administration of valproic acid in pregnant women can also cause neural tube defects in the fetus.

8 At his next visit, “Roller-coaster’s” symptoms seem to be well controlled with valproic acid, but his liver enzymes are markedly elevated. The valproic acid is discontinued, and he is prescribed another anticonvulsant that may also cause a leukopenia or agranulocytosis but is not hepatotoxic. What drug was he likely given?

Carbamazepine, which is really only effective in acute manic episodes, is known to produce a persistent leukopenia. Therefore, regular monitoring of laboratory values would be required.

9 Why should valproic acid be used with extreme caution in patients also taking phenobarbital?

Valproic acid inhibits the hepatic metabolism of phenobarbital and displaces phenobarbital from plasma proteins. These effects result in elevated levels of free plasma phenobarbital, putting the patient at risk for barbiturate-induced coma.

10 In someone with a seizure disorder that is well controlled with phenytoin, why may the addition of carbamazepine cause seizures to occur again?

Carbamazepine induces hepatic enzymes, which increase the metabolism of phenytoin and can reduce its plasma level to subtherapeutic levels.

Summary Box: Bipolar Disorder

Bipolar I disorder is defined as one or more manic or mixed episodes (major depressive episode is not required).

Bipolar II disorder consists of one or more major depressive episodes and at least one hypomanic episode.

Cyclothymia describes many episodes of depression and hypomania occurring over a 2-year period.

Lithium has a narrow therapeutic index.

Side effects of lithium include nephrogenic diabetes insipidus and hypothyroidism.

Valproic acid is now the mood stabilizer of choice due to side effect profile and lower toxicity.

Valproic acid is more effective than lithium in rapid-cycling and mixed-state episode bipolar disorder.

Case 16-3

A 48-year-old man complains of poor appetite, insomnia, decreased interest in activities that he used to enjoy, difficulty concentrating, and loss of energy for much of the past year. He has lost 20 lb in the past 6 months. He denies illicit drug use or alcohol abuse and is not taking any prescription medications. Physical examination is unremarkable. Laboratory evaluation reveals a normal TSH and T₄.

1 What is the most likely diagnosis?

Major depressive disorder is most likely. However, the differential diagnosis for depression includes hypothyroidism, bipolar, schizophrenia, Parkinson’s disease, chronic renal failure, anemia, dementia, substance withdrawal, and anxiety.

2 According to the DSM-IV, what criteria must be met in order to make the diagnosis of major depressive disorder?

Major depressive disorder can be diagnosed when at least five of the following symptoms are present on an almost daily basis for at least the past 2 weeks, and when at least one of the symptoms is either depressed mood or loss of interest or pleasure in activities that were previously enjoyable (anhedonia):

1. Depressed mood most of the day

2. Anhedonia

3. Significant change in weight or appetite

4. Insomnia or hypersomnia nearly every day

5. Psychomotor agitation or retardation nearly every day

6. Fatigue or loss of energy nearly every day

7. Feelings of worthlessness or excessive/inappropriate guilt

8. Diminished ability to think or concentrate

9. Recurrent thoughts of death, suicidal ideation with or without a plan, or a suicide attempt

In addition, these symptoms must cause significant impairment in social, occupational, or other important areas of functioning. These symptoms cannot be better explained by a general medical condition (e.g., hypothyroidism), substance abuse, or loss of a loved one (bereavement).

3 What does the monoamine deficiency theory propose with respect to the etiology of depression?

A deficiency in any one of the neurotransmitters norepinephrine, dopamine, or serotonin can result in depression. There is accumulating pharmacologic evidence in support of this theory because increasing central activity of serotonin, norepinephrine, and dopamine, either individually or in combination, has been shown to be beneficial in the treatment of depression.

Step 1 Secret

For Step 1 and for your clinical years, it will be important to remember which neurotransmitter levels are altered in various psychological and neurologic diseases because treatment is generally aimed at correcting these abnormalities. You can remember which neurotransmitters are affected in depression by considering our poor friend Ned. NeD’S DOWN because he has DEPRESSION. Ne = norepinephrine, D = dopamine, S = serotonin, and DOWN refers to decreased levels of all three of these neurotransmitters in depressed patients.

4 Why does hypothyroidism have to be ruled out in this patient?

Hypothyroidism can produce symptoms similar to those of depression.

5 What pharmacologic therapies are available to treat depression?

Tricyclic antidepressants (TCAs)

Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, paroxetine, sertraline)

Monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine)

Serotonin/norepinephrine reuptake inhibitors (SNRIs) (e.g., venlafaxine, duloxetine)

Mixed serotonin reuptake inhibitor–serotonin receptor antagonist (e.g., nefazodone, mirtazapine)

Note: Electroconvulsive therapy (ECT) and psychotheraphy are other options. ECT is a very safe and effective treatment for depression and is the therapy of choice when there is a high risk of suicide, the patient has been refractory to pharmacotherapy, or there is insufficient time for a trial of medication. ECT has a response rate of 90% compared with 70% for pharmacotherapy, the main side effect being anterograde amnesia. After ECT, combined pharmacotherapy and psychotherapy is the most effective treatment.

6 On review of systems he expresses concern about a history of premature ejaculation. What class of antidepressant may help address this concern?

SSRIs commonly produce sexual dysfunction and delayed ejaculation in men. In a patient with premature ejaculation, however, the effects of delaying ejaculation would be desirable.

7 Why have the selective serotonin reuptake inhibitors become first-line treatments for depression over the tricyclic antidepressants?

SSRIs have become a first-line treatment because of their more benign side effects and because they present less danger in overdose relative to the TCAs. TCAs cause anticholinergic, orthostatic hypotensive, and sedative side effects and in overdose can cause cardiac arrhythmias, convulsions, and even coma or death. Although SSRIs can cause sexual dysfunction (delayed orgasm or even anorgasmia), this is a relatively benign side effect compared with the side effect profile of the TCAs. When treating a severe depression with TCAs, one must also consider that they are quite lethal in overdose. A patient with a suicide plan may save up the medication and subsequently overdose on it. Their toxic potential makes this a very real potential, whereas SSRIs are quite safe, even if ingested in large quantities.

8 Why might you want to avoid administering selective serotonin reuptake inhibitors and other antidepressants to this patient if his history was also significant for manic episodes?

He may have bipolar disorder, and antidepressants could precipitate a manic episode. This may happen in approximately 3% to 5% of bipolar patients.

9 What class of antidepressant was this man likely started on if he experienced symptoms of dry mouth, blurred vision, constipation, orthostatic (postural) hypotension, urinary retention, and memory impairment?

TCAs have strong anticholinergic side effects (e.g., dry mouth, blurred vision, urinary retention) and antiadrenergic side effects (e.g., orthostatic hypotension). TCAs should be used with caution in elderly patients because the orthostatic effects may increase the risk for falling with the potential for a hip fracture. Nortriptylene and desipramine have the least sedative, orthostatic, and anticholinergic side effects of the TCAs.

Note: The anticholinergic effects of the TCAs (urinary retention) make them effective for treating enuresis (bed wetting). Imipramine is usually used for this (in children and adolescents).

10 Assume that this patient responded well to some form of antidepressant therapy but then presented to the emergency room 3 weeks later suffering from priapism. What antidepressant was he likely given?

Trazodone can cause this rare but rather serious complication in men. Trazodone and nefazodone are both mixed serotonin reuptake inhibitors–serotonin receptor antagonists; remember these two drugs as being in the z-group because they both have z’s and the patient gets very sleepy (i.e., they are very sedating) from taking them.

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