Fourteen-Pound Fluvoxamine-Associated Weight Gain in a Young Woman with Depression and Multiple Anxiety Symptoms

Chief Complaint and Presenting Problem

T. was a 21-year-old young woman living at home following college graduation with diagnoses of major depressive disorder (MDD), recurrent episode, moderate; obsessive-compulsive disorder (OCD); persistent motor tic disorder; and generalized anxiety disorder (GAD) referred for worsening mood in the context of chronic anxiety, tics, and residual OCD symptoms precipitated by an interpersonal stressor.

History of Present Illness

At the time of her presentation, T. reported a 6-year history of intermittent depressive symptoms, always in the context of a controlling relationship. In the several months preceding evaluation, she reported worsening of mood, poor sleep with middle insomnia, decreased appetite without weight loss, low energy, and feelings of worthlessness upon breaking off her relationship. She also reported ruminations about this prior relationship. She was being treated with venlafaxine, 375 mg, daily for several years, which she reported helped her OCD and tics, but not her mood. Mirtazapine, 7.5–15 mg, nightly and lamotrigine, 100 mg, daily were added 2 months before she was referred for evaluation to address her symptoms. Mirtazapine, 15 mg, helped her insomnia, but caused sedation, and her symptoms otherwise persisted. It is noted that in the past, she has lost weight when depressed, although as stated that was not the case during this episode.

Additionally, T. reported a long history of worrying. At the time of evaluation, she was concerned about getting a job and how she would move into the city. She was restless with some irritability and muscle tension and had chronic stomachaches. She reported that her anxiety and depression often coexisted, but that of late she was more sad than worried.

With regard to OCD symptoms, T. reported that as a child, she had concerns about germs and contamination and experienced handwashing and counting compulsions. Her symptoms worsened in high school, but following exposure and response prevention (ERP) therapy, they diminished markedly. There were some residual contamination obsessions that she learned to identify early.

T.'s tics had been present since kindergarten. She reported numerous motor tics throughout her life, which have waxed and waned. She briefly tried guanfacine in childhood, but stopped due to sedation. There was also a brief trial of haloperidol, 0.5 mg, at age 20, which did not help. At this time, she complained of jaw popping and eye blinking. Her tics had not caused academic problems, but did result in interpersonal and family distress.

T.'s mood was her biggest concern, and given her modest response to venlafaxine over several years, a decision was made to cross-taper this medication with fluvoxamine while maintaining lamotrigine. Mirtazapine was stopped as T. reported that the dose needed for insomnia relief also caused sedation. Over 1 month, venlafaxine was tapered, while fluvoxamine was titrated up to a final dose of 250 mg of the controlled release formulation. She engaged in weekly psychodynamic psychotherapy.

T. reported an improved mood and decreased rumination. Her anxiety diminished as did her stomachaches, and she started a temporary job while she continued to search for one in her area of interest. Her tics remained stable. Seven months later, her mood had brightened, but her tics persisted and were more bothersome to her. Fluvoxamine was decreased to 200 mg in hopes of maintaining mood benefits while minimizing any selective serotonin reuptake inhibitor (SSRI) contributory effects on her tics. T. also reported feeling more tired on 250 mg, symptoms that resolved on the decrease to 200 mg. Two months later, T. expressed a desire to taper her lamotrigine dose. By this time, she had earned a job and moved into the city and her mood remained bright. Lamotrigine was uneventfully tapered over the next month.

Eighteen months into treatment, T. reported gaining 14 pounds since starting fluvoxamine, confirmed by the office scale. This increase was affecting her self-esteem and social life. She had changed her oral contraceptive pill to a copper intrauterine device (IUD) 3 months earlier, but continued to gain weight. She had always exercised and cooked a healthy diet for herself. Medical workup, including thyroid panel, was negative; her weight gain persisted.

Over the next 2 months, fluoxetine and fluvoxamine were cross-tapered and she continued on fluoxetine, 60 mg, daily. Eight weeks following the taper, she lost all 14 pounds and was back at her baseline weight. T. denied any changes in appetite or eating habits. Her psychiatric symptoms remained stable.

Past Psychiatric History

T. had been treated by numerous mental health clinicians since childhood, starting with a school psychologist in elementary school. In high school, she received cognitive-behavioral therapy, which she reported was helpful for her mood and anxiety symptoms. In college, she had brief ERP therapy as part of a research study, which was effective.

Developmental History

T. was the product of a full-term uncomplicated pregnancy. She had one younger brother and grew up in a suburb just outside of a large metropolitan area. She met all of her developmental milestones early or on time. She reported a happy childhood, noting some sibling rivalry, which she did not feel was out of the normal range.

Educational History

T. was in a regular education public school setting through high school where she excelled academically. She attended a highly renowned academically competitive college.

Social History

T. had numerous friends and was active on sports teams. She had been in what she described as a controlling relationship with a romantic partner since her junior year of high school and had recently ended it.

Family History

The younger brother was diagnosed with attention-deficit/hyperactivity disorder, which had responded well to lisdexamfetamine. One parent was reported to have some OCD tendencies and the other parent some anxiety. A maternal aunt had anxiety and depression. There was no other family history of depression, anxiety, OCD, tics, or neuropsychiatric illness.

Medical History

T. was a healthy young adult whose height and weight were appropriate with a body mass index (BMI) of 19.8. She reported irritable bowel syndrome and gastroesophageal reflux disorder. At age 14, she had mononucleosis.

T. was allergic to penicillin, Bactrim, and nitrofurantoin.

Medication History

From age 17 to 19, T. was treated with sertraline up to 300 mg daily for mood, anxiety, and OCD symptoms. This medication not only had modest benefits but also caused abulia. A trial of citalopram, 40 mg, was not effective and also caused abulia, and the same was true for escitalopram. At one time, bupropion, 150 mg, was added to her SSRI with no benefit. A trial of clonazepam at age 21 led to worsening depression. She could not recall trials of fluoxetine, fluvoxamine, or paroxetine. She had been treated with venlafaxine since age 20, up to 375 mg, which was helpful for OCD and tics.

As noted in the history of present illness (HPI), mirtazapine and then lamotrigine were added in the prior 2 months to address her depression. Her medications included Junel Fe 1/20 oral contraceptive pills; venlafaxine, 375 mg, daily; mirtazapine, 7.5–15 mg, nightly; and lamotrigine, 100 mg, daily.

Mental Status Examination

Mental status examination revealed a cooperative and polite young woman who readily engaged and was forthcoming. Her eye contact and relatedness were excellent. She was appropriately dressed. Her gait was normal. Of note were 2+ frequency 2+ intensity motor tics, including facial grimaces, glabellar wrinkling, and lateral jaw movements with occasional eye blinking. Her speech was normal.

Her thought process was goal directed and the content focused on her recently ended relationship and the effect he had on her self-worth. She reported sadness and her affect was congruent, although reactive with some desire to please. There was no suicidal or homicidal ideation. There were no auditory or visual hallucinations. She was oriented with an excellent attention span and strong fund of knowledge.

Brief Formulation

In summary, T. was a 21-year-old young woman with MDD, OCD, GAD, and a persistent motor tic disorder referred for worsening mood and depressive symptoms in the context of residual OCD, anxiety, and tic symptoms precipitated by ending a difficult relationship. From a biopsychosocial model, a family history of mood and anxiety symptoms conferred a genetic predisposition. Psychosocially, T. was a bright and competent woman on a positive trajectory. It was clear that her relationship had a negative effect on her self-esteem and sense of worth. Additionally, she had recently graduated from college and was transitioning to living back at home while looking for a job. Identity was a major developmental task for her at the time. Her mood symptoms were most bothersome to her and required intervention.

T.'s strengths included her intelligence, strong attachments, endearing nature, and wish to be helped.

Diagnoses

Medical

Discussion

This case highlights the possibility of significant weight gain with fluvoxamine and implications for treatment. The risk of weight gain is an important consideration in examining tolerability and adherence to antidepressant medications. In a patient survey that examined the primary reasons for noncompliance and treatment discontinuation with antidepressants, 43% reported weight gain as the primary factor (Ashton et al. 2005). It is often difficult to quantify the degree of weight gain as a result of antidepressant treatment because depression is often characterized by significant changes in energy and appetite. Weight gain itself can be indicative of recovery (Uher et al. 2011). In this case, T. endorsed decreased appetite on initial evaluation, but denied recent weight loss or weight changes before initiation of fluvoxamine. Before starting fluvoxamine, T weighed 130 pounds with a BMI of 19.8. After 18 months of treatment, T. reported gaining 14 pounds (BMI 21.9), an overall increase of 10.6%.

Significant weight gain during the acute phase of treatment or weight gain that continues despite resolution of depressive symptoms is concerning as a potential, but not necessarily an anticipated adverse effect of antidepressant medications (Uher et al. 2011). In T.'s case, other contributing factors were ruled out, such as underlying medical illness or major changes in diet or exercise. It is possible that her change from an oral contraceptive pill to a copper IUD contributed to some attenuation of weight gain, although her weight gain had persisted for 3 months following this change and did not begin to decrease until the medication was tapered. As a result, T. was cross-tapered from fluvoxamine controlled release, 200 mg, to fluoxetine, 60 mg. Fluoxetine was chosen given its robust evidence base and the fact that T. could not recall trying this medication in the past. After 8 weeks of treatment, she returned to her baseline weight.

A comprehensive review and meta-analysis of 116 studies of antidepressants and body weight revealed that paroxetine and fluoxetine seem to have the most significant associations. Paroxetine produced the greatest long-term increase in body weight, particularly observed after 8 months of treatment (Fava et al. 2000). This effect is thought to be due to paroxetine's affinity to cholinergic receptors. During acute treatment, a number of SSRIs (citalopram, fluoxetine, and sertraline) were associated with weight loss to various extents. Fluoxetine in particular has been clinically proven to be a potent anorexigenic drug, but with transient effects, as restoration of weight may occur during the maintenance period. Interestingly, there are currently very limited data on fluvoxamine with regard to changes in weight (Serretti and Mandelli 2010).

A point to consider is that T. was cross-tapered from fluvoxamine to fluoxetine, an SSRI that appears to have the most evidence for acute weight loss. The anorexigenic effects of fluoxetine may have facilitated the return to T.'s baseline weight, although she denied any changes in her appetite. In this particular case, there appeared to be a temporal correlation with the cross-taper of fluvoxamine with fluoxetine and the concomitant weight loss.