My Life is Hell, Doc. Please Help Me!

TALES FROM THE CLINIC

In this installment of Tales From the Clinic: The Art of Psychiatry, we visit a case of severe anxiety in a young man who otherwise presents as the perfect patient who is treatment adherent. Individuals with anxiety suffer pervasive impairment in everyday life, and treatment is often not fully effective. Somatic and physical comorbidities typically complicate clinical anxiety presentation, but there are exciting conceptual and treatment considerations in this field worth highlighting, including novel concepts such as gut microbiome influence on anxiety disorders, high body awareness, and somatosensory amplification dimensions.

Case Study

“Mr West,” aged 30 years, is a well-groomed, soft-spoken man who presents to the clinic for anxiety. He gives you access to extensive medical records spanning the past 8 years, during which time he has received treatment for generalized anxiety. He complains of intense anxiety, fatigue, and hopelessness on a daily basis. According to the patient, his symptoms are comparable with a “living hell on earth.” Mr West had a history of illicit drug use—stimulant use—for a brief period in his early 20s but has not relapsed since. He describes a rich cultural background with life in different countries (accompanying his family as they moved), as well as medications and illicit substance use that are unfamiliar to you, prompting some frantic internet searching. At one point, he mentions fenethylline, which he felt had helped him “fight being tired,” but says he has not used it in about 7 years.

To tackle anxiety symptoms, he has been on a plethora of medications, all of which had adverse effects (AEs) and were discontinued. He has been fully adherent to all treatment recommendations, has never missed any of his appointments, and produces multiple negative urine drug screens. He is diligent in attending all of his psychotherapy sessions as well. Despite his symptoms, he maintains a job, pays his bills with no issues, and dedicates a lot of attention to his ailing mother. However, you note upon history-taking that he has no close friends and has not had romantic involvements, which he attributes to his symptoms: “I’m just not OK, doc, I tell you.” The patient is followed for 6 years.

Year 1: Getting to Know the Patient

The first year is spent establishing rapport and getting to know the patient. Monthly visits follow the same pattern: The patient profusely describes beliefs of having “something wrong” that is not properly diagnosed. He asks for brain imaging and cortisol levels, and he brings literature showing sustained brain damage from substance use. Attempts at reassurance often fall flat and are of limited effectiveness, but, as he is a model patient otherwise, you keep trying. Attempts at cognitive behavioral therapy produce limited positive effects, and the patient frequently comments, “This is too simple for me.”

You believe, based on his description, that he has irritable bowel syndrome (IBS), but he has not received specialized care. He reports that the fatigue and anxiety correlate with his gastrointestinal (GI) symptoms. He does slightly better when he is able to wake up between 9 and 10 AM; when he has to awaken earlier (ie, for work), he experiences loose bowels, burping, indigestion, and nausea.

At the end of year 1, Mr West tells you he has to seek “more care. I have to get answers—something is wrong with me.” He moves to another country in the hopes of more thorough treatment. He returns in 2 years, and you are surprised to see his name appear on your clinic roster.

Years 3 and 4: The Return

Out of the blue, Mr West returns, bringing with him a panoply of medical test results, all of which are negative, as expected. He continues to report that he feels he has a terrible missed diagnosis, but he is less forceful in that statement and more amenable to reassurance. He continues to report daily GI symptoms and fatigue that severely limit his social interactions. Mr West mentions 2 medications that have been somewhat helpful, both of which you had to Google: Motival (fluphenazine and nortriptyline) and Deanxit (melitracen and flupentixol). He continues to take fluoxetine, as he has done for years.

Year 5: Addressing GI Issues

In year 5, Mr West agrees to go to a GI specialty clinic. As a result, he changes his diet drastically, with partial anxiety improvement. However, he continues to complain of daily tinnitus. He continues to use medications not available in the United States. As you look for alternatives available here, you start him on lisdexamfetamine, which he feels is helpful with fatigue. At most sessions, however, he still reports his life is hell.

Exploring Epidemiology

Generalized anxiety disorder (GAD) is characterized by exaggerated tension, worrying, and nervousness about daily life events. GAD is often a lifelong disease, causing significant impairment.¹ The prevalence of anxiety disorders in the United States is approximately 10% in adults¹ and 19.1% in adolescents (Figures 1 and 2).² Symptoms include restlessness, irritability, and fatigue, with overthinking and consideration of worst-case scenarios predominating cognitive schemas of GAD patients. Patients with anxiety frequently have GI symptoms (about 18% of individuals).³ Individuals with IBS are twice as likely to have physical fatigue, GI-specific anxiety, perceived stress, pain catastrophizing, and trait anxiety.⁴ More severe mental symptoms and distress are associated with IBS severity, and vice versa.⁵

Diagnosis and Treatment

Computational modeling confirms what clinicians already know: Evidence suggests that individuals with psychiatric illness such as depression and anxiety misread and misinterpret visceral information compared with healthy controls.⁶ As a result, a patient with anxiety may feel a benign physical symptom very acutely and interpret the symptom in a catastrophizing way, instead of dismissing it as normal. A relevant concept is body awareness.⁷ Somatic internal perceptions—which are often preconscious—involve interoception and proprioception, and these neurological paths can be altered or damaged by disease processes. Those sensations arrive to consciousness and are interpreted by the individual, with an assigned explanation for the sensation in question. Thus, when dealing with patients who have anxiety and comorbid somatic symptomatology, the clinician may be faced with somatosensory amplification and potential exaggerated or maladaptive interpretation of bodily symptoms. This is a budding research field, with further definitions and clarification of terminology needed.

Patients with anxiety disorders have a tendency to avoid making changes to their medications, as trying new things and making alterations to their routine makes them apprehensive. This may make them more likely to report AEs after trying new treatment options, which could explain why this patient had low symptomatic tolerance to many of the attempted alternate treatments. It is important to give patients with anxiety disorders ample time to adapt to changes in their treatment regimens. Forcing change, or switching too rapidly, may be counterproductive and could create apprehension, possibly worsening anxiety and creating a barrier to adherence. Slow dosing and upward titration are essential to avoid AEs and a mental aversive reaction to treatment.

Treatment Selection

It is sometimes difficult to unravel all aspects of a clinical case within a few visits. Intrinsic personality aspects can underlie much of the behaviors we label as anxiety; this includes neuroticism.⁸ For example, the patient’s mother had possible paranoid traits, chronically thinking that the neighbors made noise to bother her. Therefore, paranoia in this patient may be part of the family’s disposition, further explaining response to agents containing low-dose antipsychotics. Anxiety and depression tend to be highly comorbid, so it should be a priority to screen for and treat both as part of the treatment plan.

For anxiety disorders, guidelines usually recommend a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor as first-line treatment,^9,10 with augmenting agents such as the azapirones (like buspirone) and antihistamines (like hydroxyzine). Only 1 antipsychotic—trifluoperazine—is approved by the US Food and Drug Administration for use in treating anxiety, although off-label use of multiple antipsychotic agents is very prevalent in clinical practice.¹⁰ GABAergic agents are also profusely used with some success. Serotonergic mechanisms are important, given the presence of serotonin receptors throughout the gut and the known dysregulation of serotonergic afferent neural signals in functional GI disorders.¹¹

In terms of dosing, clinicians anecdotally note that some patients with anxiety seem to require multiple doses of medications, even for those agents that can be dosed once daily. This is another clinical correlate of anxiety that may be unrelated to treatment, but more linked to patient satisfaction, as systematic reviews show that most classes of psychotropics can be dosed once daily without a decrease in efficacy.¹²

In this case, the patient did well on Deanxit and Motival, each of which combines an antipsychotic medication and an antidepressant medication. A positive response to Deanxit and sertraline vs sertraline alone has been shown in patients with chronic somatic diseases, so this could explain the success of the regimen in this patient.¹³ Mr West continued to be stressed about having to ask people to get his medication when they travel and wanted a substitute. He achieved the best results with chlorpromazine, which is chemically similar to the flupentixol in Deanxit.

Concluding Thoughts

Psychotherapeutic interventions are crucial in anxiety disorders in general, not just GAD. Symptomatic improvements of more than 50% can be achieved with cognitive-behavioral therapies, meta-cognitive therapy, mindfulness-based cognitive therapy, and acceptance and commitment therapy.¹⁴

Lastly, lifestyle factors such as exercise (eg, running) are underemphasized and underused modalities of treatment that have shown to be helpful in decreasing depression and anxiety,¹⁵ and they should be strongly encouraged. Diet modification, whether the patient has GI symptoms or not, is also relevant, as multiple studies now highlight the role of gut microbiome in depression/anxiety disorders.¹⁶

Dr Mourani is a volunteer research fellow in the Department of Psychiatry at the American University of Beirut. Dr Moukaddam is an associate professor in the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, as well as the Ben Taub Adult Outpatient Services director and the medical director of the Stabilization, Treatment & Rehabilitation (STAR) Program for Psychosis, also at Baylor College of Medicine. She also serves on the Psychiatric Times^TM Advisory Board.

References

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2. Ries Merikangas K, He J-P, Burstein M, et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication—Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry. 2010;49(10):980-989.

3. Mussell M, Kroenke K, Spitzer RL, et al. Gastrointestinal symptoms in primary care: prevalence and association with depression and anxiety. J Psychosom Res. 2008;64(6):605-612.

4. Midenfjord I, Borg A, Törnblom H, Simrén M. Cumulative effect of psychological alterations on gastrointestinal symptom severity in irritable bowel syndrome. Am J Gastroenterol. 2021;116(4):769-779.

5. Söderquist F, Syk M, Just D, et al. A cross-sectional study of gastrointestinal symptoms, depressive symptoms and trait anxiety in young adults. BMC Psychiatry. 2020;20(1):535.

6. Smith R, Kuplicki R, Feinstein J, et al; Tulsa 1000 Investigators. A Bayesian computational model reveals a failure to adapt interoceptive precision estimates across depression, anxiety, eating, and substance use disorders. PLoS Comput Biol. 2020;16(12):e1008484.

7. Mehling WE, Gopisetty V, Daubenmier J, et al. Body awareness: construct and self-report measures. PloS One. 2009;4(5):e5614.

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9. Penninx BWJH, Pine DS, Holmes EA, Reif A. Anxiety disorders. Lancet. 2021;397(10277):914-927.

10. Garakani A, Murrough JW, Freire RC, et al. Pharmacotherapy of anxiety disorders: current and emerging treatment options. Front Psychiatry. 2020;11:595584.

11. Del Colle A, Israelyan N, Gross Margolis K. Novel aspects of enteric serotonergic signaling in health and brain-gut disease. Am J Physiol Gastrointest Liver Physiol. 2020;318(1):G130-G143.

12. Kikuchi Y, Shimomura Y, Suzuki T, et al. Single versus multiple daily dosing regimens of psychotropic drugs for psychiatric disorders: a systematic review and meta-analysis. J Clin Psychiatry. 2021;82(2):20r13503.

13. Wang L, Zhong Z, Hu J, et al. Sertraline plus deanxit to treat patients with depression and anxiety in chronic somatic diseases: a randomized controlled trial. BMC Psychiatry. 2015;15:84.

14. Apolinário-Hagen J, Drüge M, Fritsche L. Cognitive behavioral therapy, mindfulness-based cognitive therapy and acceptance commitment therapy for anxiety disorders: integrating traditional with digital treatment approaches. Adv Exp Med Biol. 2020;1191:291-329.

15. Vieira Pereira H, Labisa Palmeira A, Encantado J, et al. Systematic review of psychological and behavioral correlates of recreational running. Front Psychol. 2021;12:624783.

16. Simpson CA, Diaz-Arteche C, Eliby D, et al. The gut microbiota in anxiety and depression – a systematic review. Clin Psychol Rev. 2021;83:101943. ❒