Chapter 5 -HD Physician's Guide To HD

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 "understandable" 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 "understandable," 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	IO-ZOmg	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-ZOOmg	dry mouth, blurry vision, constipation, hypotension, tachycardia, sedation
Other	Nefazodone	50-IOOmg	450-600mg	sedation, nausea, dry mouth, dizziness, constipation
	Buproprion	100-ZOOmg	300-450mg	seizures, agitation, dry mouth, insomnia, nausea
	Venlafaxine	25-37.5mg	225 mg	hypertension, nausea, headache, constipation

 

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

 

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.