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:   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), nefazadone (Serzone), paroxetine (Paxil), amitriptyline (Elavil), and trazedone (Desyrel) have sedative effects in some patients. Mirtazapine (Remeron) and doxepin (Sinequan) are used most commonly for this purpose. There are always exceptions, since a drug that is stimulating to one patient may be sedating for someone else. The wakefulness-promoting agents, modafinil (Provigil), and the psychostimulants are also quite effective wakefulness-promoting agents in some patients. Administering a psychotropic that is stimulating in the morning and/or one that is sedating at night have an additional and additive benefit that may further normalize the circadian rhythm.

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. Risperidone (Risperdal) may be particularly effective in treating these symptoms in children and adolescents. Quetiapine (Seroquel) may be quite effective in treating paranoia and insomnia. Ziprasidone (Geodon) may be effective when considerable apathy is present.

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.