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Physicians Guide to the Management of Huntington's Disease
 
Depression

Introduction

Patients with Huntington's disease who have psychiatric disorders generally suffer from underdiagnosis and undertreatment. It is important to remember that psychiatric problems, particularly depression, are very common and very devastating in HD, but they are also very treatable. Relieving a depression in some-one with HD may be the single most effective intervention a physician can perform.

 Psychiatric disturbances in HD are varied. Some patients suffer from conditions such as Major Depression, Bipolar Disorder, or Obsessive-Compulsive Disorder which are specific well-described syndromes, found in all sorts of patients.

Many, if not most people with HD also experience less well defined, non-specific changes in personality and mood, such as irritability, apathy, or disinhibition. Most of these psychiatric problems are believed to be related directly to the central nervous system injury caused by HD. This issue is discussed further in the chapter on cognition.

Depression

"Who wouldn't be depressed if they had HD?" Actually, research and clinical experience shows that many HD patients are not depressed, and are able to adapt gradually to having HD. Nonetheless, even severe depression in someone with HD is often explained away as an "understand-able" reaction, therefore not requiring additional treatment.

This potential for overinterpretation exists in a variety of other serious medical conditions such as AIDS, stroke, and Aizheimer's disease, which have a high comorbidity with depression. In fact, those patients who have a depressive syndrome, even when the depression is "understand-able," and even when there are clear triggers, usually respond to standard treatments, including medications and psychotherapy.

Because depression in HD appears directly related to the brain disease, pharmacotherapy is usually indicated.

TABLE 11: Signs and Symptoms of Depression
  • Depressed or irritable mood
  • Loss of interest or pleasure in activities
  • Change in appetite, or weight loss
  • Insomnia or hypersomnia
  • Loss of energy
  • Feelings of worthlessness or guilt
  • Impaired concentration
  • Thoughts of death or suicide
  • Loss of libido
  • Feelings of hopelessness
  • Social withdrawal
  • Psychomotor retardation or agitation

(Based on DSM-IV criteria)

Major Depression is a clinical syndrome, a constellation of signs and symptoms which, taken together, suggest the diagnosis. Use of diagnostic criteria helps to distinguish major depression from demoralization, transient changes in mood caused by negative life events, such as bereavement, and from some of the symptoms of HD itself, such as weight loss, trouble with concentration, and apathy.

Patients with Major Depression have a sustained low mood, often accompanied by changes in self-attitude, such as feelings of worthlessness or guilt, a loss of interest or pleasure in activities, changes in sleep, particularly early morning awakening, and appetite, loss of energy, and hopelessness. Depressed patients often feel worse in the morning than in the afternoon.

In severe cases of depression, patients may have delusions or hallucinations, which tend to match their depressed mood. A patient may hear voices berating him or urging him to commit suicide, or may have the delusion that he will be going to jail, or that he has killed his family.

Depressed patients often display psychomotor retardation, a slowing of speech and movement as a result of depression. In extreme cases they can appear stuporous or catatonic.

It is important to remember that because depression is a syndrome, with various symptoms and manifestations, the presenting complaint may be something other than a low mood. For example a depressed patient may complain of insomnia, anxiety, or pain, with each problem only a symptom of the depression which is the underlying cause.

It is vital to get the whole story, because symptomatic treatment for any of these complaints, e.g. sleeping pills, tranquilizers, or narcotics, could be worse than no treatment at all.

A specific complaint of depressed mood is not necessary to make the diagnosis if the patient has the other symptoms. In fact patients with HD often have trouble identifying or describing their emotional state. Depression in such a patient may be characterized by changes in sleep or appetite patterns, agitation, tearfulness, or a drop-off in functional abilities. In such circumstances the diagnosis should be considered.

 

In evaluating an HD patient with depression the physician also needs to consider whether some physical problem, other than HD, might be the cause. The patient's medical history should be reviewed for conditions such as hypothyroidism, stroke, or exposure to certain drugs associated with mood changes, such as steroids, reserpine, beta-blockers, and particularly alcohol.

Pharmacotherapy of Depression

Depressed people with HD can usually be treated with the same agents as any other patient with depression, but certain factors may make some drugs easier to use.

Many new medications have become available since the first edition of the Physician's Guide and the tricyclic antidepressants, while highly effective, should no longer be considered the standard first-line choice.

Instead, the physician should consider the Selective Serotonin Re-uptake Inhibitors (SSRIs), such as sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), and fluvoxamine (Luvox). These offer the advantages of low side effect profile, once-a-day dosing, and safety in the event of overdose.

Of these drugs, fluoxetine has a much longer half-life. If a patient develops an unpleasant side effect it will take longer to wear off. On the other hand this may make it a good choice for patients who sometimes forget to take their medicine.

TABLE 12: Key Points in the Treatment of Depression
  • Avoid overinterpretation of symptoms.
  • Depression is very common in HD. Have a low threshold for diagnosis and treatment.
  • HD patients are sensitive to side effects. Start medications at a low dose and increase gradually.
  • Ask about substance abuse.
  • Ask about suicide.

The SSRIs are sometimes stimulating and most patients should take them in the morning rather than at bedtime. Initial side effects may be Gl upset or diarrhea, and increased anxiety or insomnia (although, if they are part of a depression, these symptoms will eventually respond to the treatment).

SSRI-induced insomnia may respond to 25-50mg of trazodone (Desyrel) qhs. A small number of patients will develop sexual problems on SSRIs, particularly anorgasmia or ejaculatory delay. These symptoms are highly dependent on the dose. Some people have asserted that SSRIs, particularly fluoxetine, cause violence or suicide in psychiatric patients. There is no valid evidence to support this claim.

Patients with HD are sensitive to the potential side effects of CNS drugs. Any new drug should be started carefully, and increased gradually. Sertraline 25-50mg, paroxetine lOmg, or fluoxetine lOmg are appropriate starting doses. If well tolerated, the dose can be increased after a few days or a week to sertraline 50-IOOmg, paroxetine 20mg, or fluoxetine 20mg. Most patients will respond to these doses, but sometimes higher doses will be necessary.

As we will discuss, SSRIs may also be particularly useful for some of the more nonspecific psychiatric symptoms found in patients with HD, such as irritability, apathy, and obsessiveness.

Other, newer antidepressants we have used with success in patients with HD include buproprion (Wellbutrin), venlafaxine (Effexor), and nefazodone (Serzone). These all require dosing several times a day.

A new formulation of venlafaxine, Effexor XR, may be given once a day, and nefazodone is sometimes given in a single bedtime dose, despite the short half-life. It is often difficult for depressed patients, especially those with cognitive impairment, to adhere to a complex medication regimen. Therefore these drugs may not be good first choices if there is no responsible family member who will help make sure that the patient takes his medicine.

Tricyclic antidepressants (TCA's) such as Nortiptyline (Pamelor), Imipramine (Tofranil) or Amitryptiline (Elavil) remain an important class of drugs for depression in HD. They can be given once a day (usually at bedtime because of sedative properties). Common side effects of TCA's include constipation, dry mouth, tachycardia, and orthostasis.

We tend to favor nortriptyline over the others because of the relatively low incidence of these side effects and because of the well-established range of blood levels which have been associated with efficacy. It is not necessary to reach the target blood level if the patient has already responded to a lower dose, but the availability of meaningful blood levels for the TCA's can serve as a useful check of compliance, and a reassurance that a patient's dose is optimal.

Since TCA's can worsen conduction delays, an EKG is indicated prior to treatment if the patient's cardiac status is unknown. TCA's are extremely dangerous in overdose. As little as a week's supply may be fatal if taken at once. They are a poor choice in patients with a history of deliberate overdoses and may have to be dispensed only a few pills at a time if this is a concern.

TABLE 13: Medications Used to Treat Depression

CLASS

MEDICATION

STARTING DOSE

MAXIMUM DOSE

ADVERSE EFFECTS

SSRIs

Fluoxetine

10-20mg

60-80mg

insomnia, diarrhea, Gl upset, restlessness weight loss

Sertraline

25-50mg

200mg

similar 

Paroxetine 

10-20mg

40-60mg

similar, more sedation

Tricyclics

Nortriptyline

10-25mg

150-200mg

dry mouth, blurry vision, constipation, hypotension, tachycardia, sedation

Other

Nefazodone

50-100mg

450-600mg

sedation, nausea, dry mouth, dizziness, constipation

Buproprion

100-200mg

300-450mg

seizures, agitation, dry mouth, insomnia, nausea

Venlafaxine

25-37.5mg

225 mg

hypertension, nausea, headache, constipation

If the patient's depression is accompanied by delusions, hallucinations, or significant agitation, it may be necessary to add an antipsychotic medication to the regimen, preferably in low doses to minimize the risk of sedation, rigidity, or parkinsonism.

If the neuroleptic is being used for a purely psychiatric purpose, and is not required for suppression of chorea, the physician may want to prescribe one of the newer agents such as risperidone (Risperdal), olanzepine (Zyprexa), or quetiapine (Seroquel). These drugs may have a lower incidence of side effects and appear to be just as effective.

Among the older neuroleptics, high potency agents such as haloperidol (Haldol) or fluphenazine (Prolixin) tend to be less sedating, but cause more parkinsonism. Lower potency agents such as thioridazine (Mellaril) may aid with overactivity and sleeplessness, but tend to be constipating and can cause orthostasis.

Benzodiazepines, particularly short acting drugs such as lorazepam (Ativan) may be another good choice for the short-term management of agitation. In any case neuroleptics and benzodiazepines used for acute agitation should be tapered as soon as the clinical picture allows.

TABLE 14: SOME ANTIPSYCHQTIC MEDICATIONS USED IN HD

MEDICATION

STARTING DOSE

MAXIMAL DOSE

SIDE EFFFCTS

Fluphenazine

0.5-2.5mg

20-30mg

sedation, parkinsonism, dystonia, akathisia, hypotension, constipation, dry mouth, weight gain

Haloperidol

0.5-2.5mg

20-30mg

same

Risperidone

0.5-lmg

4-6mg

less parkinsonism, less dystonia

Olanzapine

2.5-5mg

15-20mg

less parkinsonism, less dystonia

Quetiapine

25-50mg

500-750mg

less parkinsonism, less dystonia

Electroconvulsive therapy (ECT) has also been found effective in depressed patients with HD. This treatment should be considered if a patient does not respond to several good trials of medication, or if an immediate intervention is needed for reasons of safety.

For example a severely depressed patient may be refusing food and fluids, or may be very actively suicidal. ECT may be particularly effective in treating delusional depression.

Depressed patients should always be asked about substance abuse. Substance abuse, particularly of alcohol, can be both a consequence or a cause of depression, makes treatment difficult or impossible if not addressed, and significantly increases the risk of suicide.