Clomopramine—also known by the brand name Anafranil—belongs to a class of drugs called tricyclic antidepressants. Developed in 1964 for Swiss pharmaceutical company Ciba-Geigy (now a part of Novartis), the drug was, as you may have guessed, created to treat depression, and that’s what providers first prescribed it for.
It wasn’t long, however, before clomipramine was found to help treat several other conditions. Among these were panic disorder, social anxiety disorder, generalized anxiety disorder (GAD), body dysmorphic disorder, and cataplexy (sudden muscle weakness or paralysis) in people with narcolepsy.
The disorder that clomipramine became most closely associated with, though, was Obsessive-Compulsive Disorder (OCD). Not only does clomipramine have the distinction of being the first drug investigated for and found to be effective in the treatment of OCD, but in 1989, it became the first drug to be approved by the FDA for that exact purpose.
This article aims to provide an understanding of clomipramine’s role in OCD treatment, shed some light on how it works, its efficacy, its limitations, and how it stacks up against other available therapies.
What are tricyclic antidepressants?
As you’re likely aware, an antidepressant is a medication that helps regulate mood and alleviate symptoms of depression and certain other mental health conditions by affecting the balance of chemicals in the brain. “Tricyclic” antidepressants get their name from their three-ring chemical structure. TCAs work by enhancing neurotransmission in neurons in the brain that utilize serotonin and norepinephrine.
First developed in the years after World War Two, TCAs represented a significant breakthrough in mental health treatment. Imipramine (Tofranil)—the first TCA—was approved by the FDA to treat depression in 1959. Clomipramine was approved to treat depression 15 years later in 1974, though a further 15 years elapsed before it became the first drug to receive FDA approval to treat OCD. This marked an important milestone in treating the condition while providing hope to millions around the globe.
To understand clomipramine’s significance in treating OCD, we must first understand what living with OCD entails.
OCD is a mental health condition that involves persistent, intrusive, and distressing thoughts, images, or urges (obsessions) and repetitive behaviors or rituals (compulsions). These obsessions and compulsions can take many forms. Some people might have obsessions focused on contracting or transmitting diseases and a corresponding hand-washing compulsion. Others’ obsessions could be focused on a fear that they might harm themselves or others. As a result, they might avoid being in easy reach of a knife as a compulsion.
These compulsions are intended to reduce the intense distress and anxiety that results from obsessions, or to prevent an unwanted outcome from occurring. Compulsions do offer temporary relief, but at the expense of reinforcing the “OCD cycle”—a relentless sequence of obsessions, anxiety, compulsions, and relief. When their obsessions are once again triggered, the now-strengthened cycle begins again.
While people often casually say they’re “a little OCD,” an actual diagnosis is made when one’s symptoms are especially distressing, time-consuming, or disruptive in their life. OCD’s impact is widespread: it can strain relationships, as loved ones may have difficulty understanding the compulsive behaviors. It can hinder daily activities like work, school, and socializing. Near-constant anxiety and rituals can lead to exhaustion and isolation.
Additionally, the fear of stigma surrounding mental health can make it difficult for people with OCD to get a diagnosis and begin treatment. This stigma is a big reason why, on average, people aren’t accurately diagnosed with OCD until nearly 13 years after their symptoms appear—and once a diagnosis is made, it takes another year and a half for them to access effective treatment.
One of those evidence-based, first-line treatments is called exposure and response prevention therapy (ERP). The other first-line treatment is a class of medications that affect the brain chemical serotonin, including clomipramine.
How clomipramine (Anafranil) works
Taking clomipramine changes the activity of nerve cells in the brain that use chemicals called serotonin and norepinephrine. These chemicals play a role in regulating your mood, anxiety, and other emotions.
Clomipramine works by blocking the reuptake of these chemicals in the brain. After these chemicals are released, they are reabsorbed by the nerve cells. However, clomipramine slows the rate at which this reabsorption happens.
By blocking the reuptake of these chemicals, clomipramine allows serotonin and norepinephrine to stay between the nerve cells longer. Gradually, over several weeks, this works to enhance the communication in these nerve cells. This helps improve mood and reduces symptoms of depression, anxiety, and reduces the intensity and frequency of obsessions and compulsions in people with OCD. These medication effects may also lead over time to adaptive modifications in brain circuits involved in emotion and stress response.
Comparing clomipramine with other drugs used to treat OCD
When pharmaceuticals are used to treat OCD, selective serotonin reuptake inhibitors (SSRIs) are often prescribed first due to their effectiveness and generally preferable side effect profile than TCAs. SSRIs commonly prescribed for OCD include fluoxetine, (Prozac) fluvoxamine, (Luvox), and sertraline (Zoloft). Other drugs may be considered when SSRIs fail to provide sufficient relief or are not well-tolerated.
Clomipramine is particularly effective in treating OCD symptoms and is often prescribed in cases where other medications or therapies have not provided sufficient relief. However, clinical trials that directly compare clomipramine to an SSRI generally do not find clomipramine to be more or less effective. This is echoed by a 2016 meta-analysis examining 53 articles comparing clomipramine and other medications.
This doesn’t mean, however, that clomipramine doesn’t have major potential benefits for people’s OCD treatment. Sometimes, people who don’t respond to SSRIs might respond well to clomipramine instead. Also, some may be prescribed clomipramine as an augmenting agent—a secondary medication added to an existing form of treatment, such as an SSRI, to enhance its effectiveness or address specific aspects of a condition that may not be fully responsive to the initial treatment on its own.
Side effects of clomipramine can include dry mouth, constipation, blurred vision, dizziness, drowsiness, weight gain, and sexual dysfunction. While SSRIs and SNRIs may cause similar side effects, they are generally considered to be tolerated better. An advantage of clomipramine is that blood levels can be measured, which can help guide treatment in terms of whether a person is getting a therapeutic level and making sure the levels are not too high.
Medications belonging to several classes, whether SSRIs, SNRIs, TCAs, or atypical antipsychotics, can provide a lifeline for people with OCD. For many, these drugs are most effective when used with exposure and response prevention therapy (ERP).
Exposure and response prevention therapy (ERP)
In numerous studies spanning several decades, ERP has been shown to be highly effective in managing OCD. ERP works by interrupting the vicious cycle that maintains and exacerbates OCD symptoms over time.
During ERP, you’ll work with a specially trained therapist to create a hierarchy of situations that trigger your obsessions, starting with the least distressing and progressing to the most distressing. Over time, you’ll gradually confront these situations or objects—directly or indirectly—learning to tolerate the associated discomfort and resist the urge to perform compulsions. Generally, people start to experience significant results within 12 to 20 sessions, finding themselves less distressed by their triggers and better in control of how they respond to them.
While many have recovered from OCD with ERP alone, it can be combined with SSRIs, SSRIs, TCAs, among other types of drugs, and can be tailored to meet each person’s individual needs.
Start getting better today
NOCD therapists are specially trained in delivering ERP and regularly refer members to qualified prescribers who can identify medication that may reduce their OCD symptoms. If you think that you may be struggling with OCD, I encourage you to read more about NOCD’s evidence-based approach to treating OCD.