The Psychotropic Management of
Late-Stage Lyme and
Associated Diseases
By Robert C. Bransfield, M.D.
It is challenging for patients with late-stage Lyme and associated diseases (LLAD) to remain hopeful while
experiencing a disabling illness that can impact every aspect of functioning,
that is poorly understood, that is not effectively managed by the healthcare
system, and that is not adequately covered by the insurance system. To
effectively provide assistance from a psychiatric perspective, the goal is to
implement a comprehensive view of health and disease, understand the nature of
chronic tick-borne and associated diseases, have a strong foundation in
medicine and psychiatry, understand the pathophysiology
of the somatic and psychiatric symptoms of LLAD, provide a thorough exam, and
formulate an individualized treatment plan. Since LLAD are systemic conditions
that can cause both mental and general medical symptoms, no treatment plan is
sufficient unless it addresses both the mental as well as the somatic symptoms.
It is important to remember the current APA psychiatric diagnostic system, (DSM
IV), categorizes types of mental, behavioral, and emotional symptoms by a
description of symptoms and syndromes of dysfunction, but does not sufficiently
address the cause of these symptoms and syndromes. It is a major conceptual
error to diagnose in terms of either LLAD or psychiatric illnesses,
since there may be a contributory association and/or interaction between them.
To incorporate a comprehensive view of health and disease, it is
important to consider the multi-system combined effects of both the
contributors and deterrents to disease (diagrams 1 and 2). Reference is made to
the many articles on the pathophysiology of the
somatic and psychiatric symptoms of LLAD. Also, refer to my article on the neuropsychiatric assessment of Lyme
disease at: http://www.MentalHealthandIllness.com/lymeframes.html After performing a
thorough assessment, it is then necessary to prioritize which symptoms are the
most serious and the ones that contribute most towards preventing recovery.
Effective treatment planning requires combined attention to antimicrobial
treatments, psychiatric treatments, healthy lifestyle, exercise, proper
nutrition, recuperative sleep, stress management, detoxification strategies,
family dynamics, employment or school status, financial issues, legal issues,
insurance issues, and sometimes political considerations. Any highly restrictive
or fragmented view of complex disease should be avoided. Psychotherapy is a
critical component of any effective psychiatric treatment program. However, in
this article, I shall focus upon the pharmacological aspects of treatment.
From a historical perspective, the antibiotic
treatment of tuberculosis was found to occasionally have antidepressant
effects. This discovery evolved into the development of antidepressants and
subsequently the current used psychotropics. With the
progression of scientific knowledge, it is now clear that antibiotics can
result in psychotropic effects and psychotropics have
a number of immune and other antimicrobial effects. As a result of these
interactive direct and indirect therapeutic effects, antibiotics alone may
sometimes be sufficient to treat the psychiatric symptoms of LLAD and,
conversely, psychotropics alone may sometimes be
sufficient to treat both the psychiatric and somatic symptoms of LLAD.
In a patient with a greater number of symptoms, it is
challenging to know where to start with treatment. Sir William Osler once stated, “The young physician uses ten drugs to
treat one condition, while the older physician uses one drug to treat ten
conditions.” A thorough assessment, formulation, and prioritization of symptoms
allow us to plan which symptoms are more pivotal in perpetuating the disease
process. This, in turn, allows us to prioritize the most effective intervention
and the most effective sequence of intervention strategies. In this article, I
will focus just on the psychiatric treatment of LLAD. In some instances, the
medications discussed are used according to FDA approved indications, while in
other cases their use is considered “off-label,” since it is based upon
clinical considerations and practical pharmacology rather than FDA approved
uses. Unfortunately, there are few currently approved FDA treatments for many
of the symptoms that require attention in the patients who need treatment
today. In clinical practice, all decisions are an individualized risk vs. benefit
consideration.
There are a number of neuropsychiatric
symptom complexes associated with LLAD: cognitive losses, fatigue, circadian
rhythm disorders, psychiatric symptoms, and neurological symptoms. Cognitive
symptoms, fatigue, and circadian rhythm disorders are often associated with
excessive daytime sleepiness and disorders of motivation. I will discuss these
symptoms as a group, then the psychiatric, and finally the neurological
symptoms.
Cognitive symptoms, fatigue, excessive daytime
sleepiness, and disorders of motivation are associated with a failure to
achieve the normal amplitude of the sleep-wakefulness cycle. In a state of
health, there is a deep restorative sleep at night and a high level of cortical
activation during the day. Higher amplitude of the circadian rhythm during the
day is associated with physical energy and higher levels of cortical
activation. Higher levels of cortical activation, in turn, are associated with
increasing levels of wakefulness, cognition, executive functioning, and
motivation. In addition, deep sleep at night is associated with an enhancement
of immune functioning, thus contributing to recovery from infectious disease
and other chronic illnesses. Therefore, we need to consider strategies that
restore the normal circadian rhythm, promote cortical activation during the
day, and promote restorative sleep at night. This can be achieved by the use of
medications and other treatments that are effective in any or all of these
three areas.
The broad-spectrum psychotropics
that are commonly called “antidepressants,” have impact upon gene expression in
the central nervous system (CNS) resulting in a number of effects, including
the normalization of the circadian rhythm. In addition, some of these
medications have some short-term stimulant and sedative effects. For example, venlafaxine (Effexor XR), bupropion (Wellbutrin SR), sertraline (Zoloft), fluoxetine
(Prozac), desipramine (Norpramine),
and tranylcypromine (Parnate)
may provide stimulant effects for some patients. Conversely, mirtazapine (Remeron), doxepin (Sinequan), trimipramine (Surmontil), nefaza
For purposes of treatment, cognitive functioning may
be categorized into three groups—concentration, attention, and memory. The
predominant type of dysfunction will determine the type of treatment
strategies.
Cognitive
functioning is associated with the level of cortical activation and the closely
related functions of wakefulness and motivation. Modafinil
(Provigil) is a cortical activator that specifically
promotes calm cognitive capabilities. In selected patients, it may promote
daytime wakefulness; reduce fatigue, and improve cognition, concentration,
learning, working memory, executive functioning, motivation, and productivity.
Since this can treat many of the symptoms associated with LLDA, I have
prescribed this more than any other single medication in working with these patients.
The psychostimulants are associated with both cortical and
emotional activation. There is potential for abuse, and are highly regulated.
Compared to modafinil (Provigil),
they are more effective at reducing distractibility and improving sustained
attention, but less effective at improving concentration, learning, and other
aspects of executive functioning. The psychostimulants
include methylphenidate (Metadate CD, Concerta, Ritalin), dexmethylphenidate (Focalin), dextroamphetamine (Adderall &
Dexadrine), and pemoline (Cylert). They are also effective in selected patients,
sometimes in combination with modafinil (Provigil). Other medications that may improve cognition,
but have little effect upon wakefulness, include selegiline
(Eldepryl), bromocriptine (Parlodel), and anantadine (Symmetrel).
In addition, the acetylcholine esterase inhibitors (Aricept, Exelon & Reminyl) are often helpful for the treatment of memory
impairments associated with late-stage disease.
Restful and recuperative sleep may be promoted by
various antidepressants, anticonvulsants, antihistamines, and hypnotics. The
antidepressants with sedating capabilities were discussed in this context
above. A number of anticonvulsants improve restful sleep through a variety of
mechanisms. Gabapentin (Neurontin)
is sometimes used as a hypnotic agent, tigabine (Gabatril) has been demonstrated to improve the very
important stages 3 and 4 deep sleep, and topiramate (Topamax) can be effective in reducing nightmares and
intrusive thoughts. Patients treated with topiramate
(Topamax) may notice weight loss as a common side
effect.
Psychiatric symptoms include the common and less
common psychiatric syndromes. Multiple disease states, called comorbid conditions, are the rule, rather than the
exception. Depression is the most common psychiatric syndrome associated with
LLAD. Fear and anxiety disorders, such as panic disorder, social anxiety
disorder, generalized anxiety disorder, and obsessive-compulsive disorder, are
commonly seen. In addition, low frustration tolerance, irritability, and
explosive anger may also be seen. All of the biopsychosocial
treatments used in general psychiatry apply to the treatment of these same
symptoms and syndromes seen in association with LLAD. Paroxetine
(Paxil), venlafaxine (Effexor XR), citalopram (Celexa), sertraline (Zoloft), bupropion (Wellbutrin SR), fluoxetine (Prozac), and others are commonly used. Valproate (Depakote ER) is
sometimes added for the management of anger. Zyprexa
and other “atypicals” are used in the management of
psychotic or intrusive aggressive symptoms. Risperi
It is important to note the serotonin reuptake
inhibitor (SRI) medications have pro-inflammatory effects. If LLAD were a
post-infectious autoimmune process, SRI’s would have
a negative effect upon these patients. Instead, they frequently are
therapeutic.
Common neurological symptoms include neuropathic pain, neuropathy, restless leg syndrome, and
seizures. Neuropathic pain and neuropathy may be more
commonly treated with gabapentin (Neurontin),
tigabine (Gabatril), topiramate (Topamax), valproate (Depakote ER), venlafaxine (Effexor XR), and amitriptyline (Elavil). Often, a
combination of gabapentin (Neurontin)
and venlafaxine (Effexor
XR) is particularly effective. Restless leg syndrome (RLS) may contribute to
the disruption of sleep, and may respond well to hypnotics. In some cases,
Parkinson medications, such as roprinirole (Requip) and carbidopa-levodopa (Sinemet), offer relief. Often, RLS is cured by the use of
ferrous gluconate or other iron supplements, to
achieve a ferritin level of 50 or above. Seizures are
treated using common techniques for seizure management.
Irritable gut syndrome is common in patients with LLAD. Both upper and
lower gastrointestinal symptoms may be seen. Low doses of doxepin
(Sinequan) are often effective in helping reduce
gastrointestinal spasms and hyperacidity.
When any combination of these or other somatic
symptoms are effectively treated, the patient may be able to function at a
higher level, which invariably results in a reduction of chronic stress.
Unremitting chronic stress is associated with an immunocompromised
state that deters recovery in the presence of a chronic infectious disease. It
is important to remember the normal functioning of the immune system, rather
than the presence of antibiotics, is the most effective deterrent to infectious
disease. The goal in treatment is a healthy balance between the immune system
and parasites. Complete eradication of parasites from the body can never be
achieved, nor proven if achieved. In addition, excessive eradication of
parasites would not be compatible with healthy functioning, since complex
interdependencies exist with some of these microbes.
In summary, there is a constant interaction between
the mind and the body, and we cannot treat only the mind or the body. In managing
LLAD, there are direct and indirect therapeutic effects from psychiatric
treatments, not all of which are well understood. We can improve the treatment
outcomes of LLAD by overcoming the fragmentation that has been a part of
medicine in the past, and implementing integrated treatment approaches that
include the psychiatric interventions, such as those described above.
Virginia Sherr,
M.D., F.A.P.A., is recognized and appreciated for providing peer review for
this article.