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OCD Treatment: Medication & Complementary Approaches

Written by Maria Janda, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Evguenia Alechine
Puya Yazdi
Medically reviewed by
Evguenia Alechine, PhD (Biochemistry), Puya Yazdi, MD | Written by Maria Janda, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Ordering and checking can be a symptom of OCD

Obsessive-compulsive disorder (OCD) is a relatively common mental illness. Several treatments have been studied for OCD with positive effects, including both medication and behavioral strategies. Many natural compounds, supplements, and devices are also under investigation. Read on to learn more about OCD treatment and what you can do to help yourself or a loved one who suffers from it.

OCD Behavioral Treatments

The standard treatment of OCD includes psychotherapy (“talk therapy”) and antidepressant medication.

Follow the treatment plan prescribed by your doctor carefully. Never change or discontinue the treatment without consulting your doctor.

1) Cognitive Behavioral Therapy (CBT)

CBT has proven to be an effective method for treating OCD [1].

In a meta-analysis of 16 clinical trials and 756 people, CBT was proven to improve OCD symptoms [2].

2) Exposure and Response Prevention (ERP) Method

With ERP, a patient is first exposed to triggers and then should learn skills to stop the compulsions. The exposures can be images or descriptions that are read repeatedly to desensitize patients from their obsessions. By addressing both obsessions and compulsions, ERP has been proven to be more effective than addressing either one alone [3].

Two well-researched behavioral strategies for coping with OCD include CBT and the exposure and response prevention (ERP) method.

OCD Medication

Approved Drug Treatments

1) Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatments for OCD because they have few side effects [1].

One in five patients who take SSRIs for OCD has at least a 25% reduction in symptoms compared to placebo. Most people respond to SSRIs after six weeks. However, it is recommended to try the medication for at least eight to twelve weeks to have an effect. Evidence suggests that in order to avoid relapse, about six to twelve months of therapy is necessary [4].

Head-to-head trials between several SSRIs including fluvoxamine, paroxetine, citalopram, sertraline, and fluoxetine showed no difference in efficacy [5, 6].

Each SSRI works slightly different from the other, therefore therapy is individualized to each patient’s characteristics. For example, fluoxetine may be preferred in those who forget to take their medication daily since it lingers in the body for weeks [7].

Overweight patients may benefit from either fluoxetine or sertraline since they are both associated with the lowest weight gain [8].

Citalopram can increase the risk of heart abnormalities with daily doses of over 20 mg. A recent study disproved this elevated risk to the heart. However, if an individual is suffering from heart issues, it may be in his/her best interest to avoid citalopram and use a safer SSRI [9].

A recent meta-analysis associated high doses of SSRIs with greater efficacy than low or medium doses [10].

There are limitations to SSRIs. They often do not completely resolve all symptoms of OCD, and they have a two- to three-month lag time to achieve their full effect [11].

Of note, all antidepressants have an FDA issued black box warning for their potential to increase suicidal thoughts when starting antidepressants. It is important to contact a medical provider if this occurs [12].

There are also side effects associated with SSRIs that can be remembered as the 7 S’s:

  • Stomach upset (nausea)
  • Sleep disturbances
  • Sexual dysfunction
  • Stress (mostly agitation)
  • Serotonin syndrome (caused by too much serotonin usually presents as an intense headache, flushing, muscle rigidity and diarrhea – rare)
  • Size increase (weight gain)
  • Suicidal thoughts

Similar symptoms may also occur during withdrawal when discontinuing SSRIs [13].

Selective serotonin reuptake inhibitors (SSRIs) are first-line OCD treatment. Properly prescribed, SSRIs help improve symptoms and have few side effects.

2) Tricyclic Antidepressants (TCA)

Clomipramine is a TCA and FDA-approved drug for OCD. It blocks the reuptake of serotonin, norepinephrine, and dopamine [14].

Clomipramine has fallen out of favor because there are more effective drugs with fewer side effects [14].

Non-Approved Drugs

Some people may fail to respond to the antidepressants described above. The following drugs have been tested in people with OCD, normally as an add-on to conventional medication. You may only include these drugs in your treatment plan if prescribed by your doctor.

1) Memantine

Memantine, a medication used for Alzheimer’s disease, blocks NMDA receptors, which reduces glutamate’s effects in the brain.

In a clinical trial on 38 patients, approximately 89% of those combining the SSRI fluvoxamine with memantine no longer had OCD symptoms after eight weeks compared with 32% combining it with a placebo [15].

2) Ketamine

Ketamine blocks glutamate receptors (NMDA). In a small trial on 15 untreated adults with OCD, infusion with ketamine significantly improved obsessive symptoms. Additionally, 50% still maintained this improvement one week later [16].

3) Ondansetron

Ondansetron is helpful for nausea by blocking certain serotonin receptors. In an eight-week pilot study on 42 people, ondansetron combined with fluoxetine decreased OCD symptoms when compared to the placebo [17].

4) Mirtazapine

Mirtazapine is an atypical antidepressant that increases serotonin in the brain differently from SSRIs.

In a 12-week clinical trial of 30 people taking 60mg mirtazapine, mirtazapine outperformed placebo and decreased symptoms by about 20%. A bit over half of the people improved with the treatmentm[18].

Memantine, ketamine, ondansetron, and mirtazapine have not been approved for OCD. Early findings look promising, but large-scale studies are needed.

5) Pregabalin and Gabapentin

Gabapentin and pregabalin are used for nerve pain and as anticonvulsants to prevent seizures. Because they are structurally similar to the neurotransmitter GABA, they are thought to enhance its effects [19, 20].

One study on 40 people showed that gabapentin enhanced the effectiveness of SSRIs at alleviating early OCD symptoms [21].

Similarly, pregabalin enhanced the effectiveness of conventional OCD therapy and reduced the symptoms by 26% in a case series of 12 patients. The only side effects reported were dizziness and fatigue [22].

Limited research suggests that pregabalin and gabapentin may increase the effects of SSRIs used for OCD. High-quality data are lacking.

6) Mood Stabilizers (Lamotrigine and Topiramate)

Lamotrigine and topiramate both inhibit the actions of glutamate and have been studied as adjunctive agents for OCD.

In a study, 41 OCD patients who failed their first trial of an SSRI were given topiramate or placebo with an SSRI. There was a 32% decrease in OCD symptoms in those taking topiramate group versus only 2.4% in the placebo group [23].

Although this seems promising, there is very little evidence supporting topiramate’s effectiveness, and it does have adverse effects in the brain such as paresthesias (abnormal burning or prickling sensation) [23].

Lamotrigine decreased symptoms of observable obsessions and compulsions when used along with an SSRI in a clinical trial on 51 people. The main adverse events included headaches and skin rash. Lamotrigine can cause a deadly hypersensitivity reaction in the form of a rash called Stevens-Johnsons Syndrome (SJS), so it is important to monitor closely [24, 25].

Lamotrigine and topiramate have been studied as add-on OCD medication, but large trials on their effectiveness have yet to be carried out.

7) Amphetamines

Stimulants may have a role in the treatment of OCD, especially with co-occurring ADHD. A single dose of d-amphetamine had short term benefits in resolving OCD symptoms in a small trial on 12 people [26].

In another study on 24 people, both d-amphetamine and caffeine rapidly improved OCD symptoms within a week [27].

8) Clonazepam

Clonazepam, clonidine, and clomipramine (TCAs) were compared to the control diphenhydramine (Benadryl) in a trial on 28 people. Roughly 40% of the patients whose symptoms were not resolved with clomipramine responded to clonazepam [28].

Clonazepam may be helpful in relieving symptoms of anxiety, but, it should be used with caution in patients with previous benzodiazepine or other substance abuse histories [28].

Amphetamines and clonazepam were researched in trials of small groups of people with specific OCD subtypes. Further work is needed.

9) Opioids

Opioid drugs are often effective in various mental illnesses, including promising results in treatment-resistant OCD. However, given their addictive properties, they should be used with extreme caution [29, 30].

Naloxone, a blocker of opioid receptors, exacerbated symptoms of OCD, while tramadol, which activates them, relieved OCD symptoms [31].

There are some natural ways to increase opioids.

10) Riluzole

Riluzole, which is used in ALS, decreases the neurotransmission of glutamate. Its combination with SSRIs improved the symptoms in patients with treatment-resistant OCD [32].

11) Benadryl

One study with 28 people used Benadryl (diphenhydramine) as the placebo because it was assumed to have no effect on OCD. However, Benadryl improved the symptoms [28].

No proper clinical data backs up the use of opioids, riluzole, or Benadryl in people with OCD.

Neurostimulation Treatments for OCD & Surgery

Precautions

The following treatments are being investigated for people with OCD who don’t respond to psychotherapy or medication. Because they may have serious risks and haven’t been thoroughly tested, make sure you understand all the pros and cons before undergoing these procedures.

1) Repetitive Transcranial Magnetic Stimulation (rTMS)

rTMS is a non-invasive brain stimulation technique. It introduces a magnetic field pulse to the brain, which affects neuronal activity [33].

In a meta-analysis of 10 clinical trials and almost 300 people with OCD, rTMS decreased the symptoms in approximately 35% of the patients (versus 13% for the mock treatment) [34].

The short-term side effects were localized pain, burning, prickling sensation (paresthesia), hearing changes, altered levels of blood thyroid-stimulating hormone and lactate, and hypomania (a mild form of mania).

In rare instances, high-frequency rTMS can cause seizures [33].

In 2018, the FDA cleared a deep TMS device (BrainsWay) as an adjunct in the treatment of OCD in adults.

Solid evidence supports the use of specific deep TMS protocols for treating OCD in adults.

2) Deep Brain Stimulation (DBS)

Deep brain stimulation is an invasive strategy in which electrodes are surgically implanted in the brain to send localized electric impulses has been tested for OCD in a few cases [35].

The average overall response rate to DBS was about 50%. The studies reported limited side effects and concluded that DBS was relatively safe [36].

However, the following adverse effects have been documented in a few cases [37]:

  • Bleeding in the brain (without symptoms)
  • Seizures
  • Superficial infection
  • Hypomania
  • Worsening of depression or OCD
  • Short-term sadness, anxiety, or euphoria
Deep brain stimulation is a form of invasive neurostimulation that may be an option for people with OCD who don’t respond to non-invasive therapies.

3) Ablative Neurosurgery

Two different surgical procedures that create lesions on specific parts of the brain to alter its circuitry were tested in 87 people with treatment-resistant OCD. They helped 30 to 60% of the patients [38, 39].

Complementary and Alternative Approaches to OCD

Precautions

You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for improving your OCD symptoms.

Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.

Additionally, the purported benefits of the following supplements and lifestyle interventions are only backed by limited, low-quality clinical studies, most of which used them as an add-on to conventional therapies.

There is insufficient evidence to support their use in people with OCD, but you may implement them if your doctor determines that they may help in your case. Never use these strategies as a replacement for approved medical therapies.

Supplements

Insufficient Evidence for:

1) Inositol

Inositol, a component of cell membranes, is involved in cell communication and also increases the sensitivity of serotonin receptors [40].

In a 6-week study of 10 OCD patients, 18 g of inositol improved anxiety and depression symptoms, and caused very few side effects (mostly digestive). In another trial, the same dose only enhanced the effects of SSRIs in 3 out of 10 patients with treatment-resistant OCD [41, 42].

At this dose, inositol was more effective than fluvoxamine in a clinical trial on 20 people with panic disorder. Because this drug is approved for OCD, further clinical trials comparing both treatments could shed some light on the effectiveness of inositol [43].

In a brain imaging study of 14 people with OCD, those who responded to inositol showed increased baseline activity in a brain region (left medial prefrontal region) but reduced activity after inositol treatment in other regions (left superior temporal gyrus, middle frontal gyrus and precuneus, and right paramedian post-central gyrus) when compared to non-responders [44].

Inositol supplements seemed to improve OCD symptoms in small trials. Large-scale data are needed to determine its effectiveness.

2) N-Acetyl Cysteine (NAC)

In a 12-week study of 50 people with compulsive hair pulling (trichotillomania, which is on the OCD spectrum) NAC improved the symptoms “much or very much” in 56% of the patients (compared with only 16% of the placebo group) [45].

A systematic review of four pilot trials using NAC for 12-weeks (2,400–3,000 mg/day) concluded that NAC was promising at reducing the severity of OCD symptoms and caused minimal side effects [46].

However, a more recent 16-week trial on 44 people didn’t find NAC more effective than the placebo [47].

NAC added to the effects of SSRIs (citalopram) in improving resistance to compulsions in OCD a 10-week clinical trial on 34 children and adolescents [48].

NAC is thought to work by decreasing glutamate in the synapse and increasing glutathione. Low glutathione in certain brain regions (cingulate cortex) has been found in patients with OCD [49, 50].

Data on the effects of NAC on OCD are mixed. It improved symptoms in some trials but showed no benefits in others. More research is needed.

3) Glycine

Glycine is an amino acid that reduces glutamate function in the cortical region of the brain [51].

In a 12-week study on 24 OCD patients given 60 grams of glycine as an add-on to conventional therapy, there was a minor decrease in OCD symptoms. Importantly, ten patients dropped out of the study due to the bad taste of glycine, which caused nausea in some cases [52].

Sarcosine is an inhibitor of glycine uptake, which increases the availability of this amino acid in the brain. In a clinical trial on 25 people with OCD, 8 improved their OCD symptoms after taking sarcosine [53].

4) Caffeine

In a five-week double-blind trial with 24 patients, 300 mg of caffeine was slightly more effective than 30 mg dextroamphetamine as an add-on therapy to improve OCD symptoms. All patients completed the study without adverse events [54].

The results of this study were recently replicated in a clinical trial on 62 people [55].

Glycine and caffeine showed promise for OCD in low-quality studies, but it’s still too early to draw any conclusions.

5) Milk Thistle

Milk Thistle is a plant with the flavonoid silymarin that increased the levels of serotonin in the cortex of mice [56].

In an 8-week clinical trial on 35 OCD patients, 200 mg milk thistle decreased the symptoms. However, it was less effective than fluoxetine [57].

6) Borage Oil

Borage is a plant whose flower and oil are both used for OCD. It had anti-anxiety effects similar to benzodiazepines (ex. Valium) in mice models [58].

In a 6-week trial on 44 OCD patients, 500 mg of borage extract 1x/day decreased OCD symptoms and anxiety [59].

However, borage may cause liver toxicity, diarrhea, vomiting, headaches, worsening of asthma and is not safe during pregnancy [60, 61].

8) Zinc

Scientists have discovered that zinc may play a role in inhibiting excitatory neurotransmission, and activates multiple receptors including GABA [62, 63].

Zinc was found to be 69.2% lower in mild OCD patients than non-OCD patients in a study on almost 100 people [64].

In an 8-week study on 23 OCD patients, zinc supplementation (as an add-on to fluoxetine) helped decrease obsessions and compulsions without causing adverse effects [65].

Small studies show that zinc, milk thistle, and borage oil might be helpful as add-on supplements in people with OCD, but high-quality data are lacking.

9) Iron

In a study on almost 100 people, blood iron levels were 41 – 44% lower in patients with mild and moderate OCD [64].

Low iron is also associated with higher tic severity in Tourette syndrome. Iron supplementation decreased the severity of tics over 6-12 months in a clinical trial on 57 children with Tourette. Since there is a relation between this syndrome and OCD, this suggests that iron supplementation may help for OCD as well [66].

Iron supplements in people with OCD and low iron may help, but the findings have been inconclusive.

Mind-Body Interventions

Insufficient Evidence for:

1) Exercise

In 5 pilot trials on over 150 people with OCD receiving behavioral or pharmacological therapy, a 12-week aerobic exercise intervention reduced OCD symptoms. The benefits remained for 6 months [67, 68, 69, 70, 71].

2) Meditation

Mindfulness meditation is thought to help people with anxiety to mentally avoid their triggers. A pilot study with 17 participants showed a reduction in OCD symptoms in patients who partook in mindfulness meditation [72].

Reducing anxiety may be a beneficial approach to eliminating symptoms of OCD. Read our post on the Top 31 Natural Treatments for Anxiety for more information.

Getting regular exercise and engaging in mindfulness meditation might be beneficial for people with OCD, but further research is needed.

3) Music Therapy

Music therapy helped to alleviate symptoms of obsession and anxiety in one month in a small trial on 30 patients who were all already being treated for OCD [73].

4) Acupuncture

Acupuncture increases serotonin transmission and may exert pain-relieving effects via the opioid receptor [74].

In a pilot study on 19 people with OCD, acupuncture (as an add-on therapy) improved the symptoms. However, the study compared acupuncture with the absence of treatment instead of using a proper placebo control (i.e., needles randomly placed by someone without training in acupuncture) [75].

Takeaway

The mainstay treatment of OCD includes medication and behavioral interventions or “talk therapy.”

SSRI drugs are the first-line treatment. Proven behavioral therapies include CBT and the exposure and response prevention (ERP) method. Evidence also supports deep TMS, a form of non-invasive neurostimulation.

No supplements have been proven to reduce the symptoms of OCD. Small trials suggest that some supplements may help as add-ons, including inositol, NAC, glycine, zinc, and milk thistle. However, higher-quality studies are needed since findings on their effects have been mixed.

Some mind-body interventions like exercise, mindfulness meditation, music therapy, and acupuncture may also be helpful. These approaches improved OCD symptoms in small trials when used in addition to conventional therapy.

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