pharmacodynamical

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a chronic anxiety disorder most commonly characterized by obsessive, distressing, intrusive thoughts and related compulsions. Compulsions are tasks or "rituals" which attempt to neutralize the obsessions. OCD is distinguished from other types of anxiety, including the routine tension and stress that appear throughout life. The phrase "obsessive-compulsive" has become part of the English lexicon, and is often used in an informal or caricatured manner to describe someone who is meticulous, perfectionistic, absorbed in a cause, or otherwise fixated on something or someone. Although these signs are often present in OCD, a person who exhibits them does not necessarily have OCD, and may instead have obsessive-compulsive personality disorder (OCPD) or some other condition.

Diagnostic criteria

To be diagnosed with OCD, a person must have either obsessions or compulsions alone, or obsessions and compulsions, according to the DSM-IV-TR diagnostic criteria. The Quick Reference to the diagnostic criteria from DSM-IV-TR (2000) states six characteristics of obsessions and compulsions:

Obsessions

Recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate and that cause marked anxiety or distress.
The thoughts, impulses, or images are not simply excessive worries about real-life problems.
The person attempts to ignore or suppress such thoughts, impulses, or images, or to neutralize them with some other thought or action.
The person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind, and are not based in reality.

Compulsions

Repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly.
The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts are not actually connected to the issue, or they are excessive.

In addition to these criteria, at some point during the course of the disorder, the individual must realize that his/her obsessions or compulsions are unreasonable or excessive. Moreover, the obsessions or compulsions must be time-consuming (taking up more than one hour per day), cause distress, or cause impairment in social, occupational, or school functioning. OCD often causes feelings similar to those of depression.

Symptoms and prevalence

OCD manifests in a variety of forms. Studies have placed the prevalence between one and three percent, although the prevalence of clinically-recognized OCD is much lower, suggesting that many individuals with the disorder may not be diagnosed. The fact that many individuals do not seek treatment may be due in part to stigma associated with OCD. Another reason for not seeking treatment is because many sufferers of OCD do not realize that they have the condition.

The typical OCD sufferer performs tasks (or compulsions) to seek relief from obsession-related anxiety. To others, these tasks may appear odd and unnecessary. But for the sufferer, such tasks can feel critically important, and must be performed in particular ways to ward off dire consequences and to stop the stress from building up. Examples of these tasks are repeatedly checking that one's parked car has been locked before leaving it, turning lights on and off a set number of times before exiting a room, repeatedly washing hands at regular intervals throughout the day, touching objects a certain amount of times before leaving a room, or walking in a certain routine way. Physical symptoms may include those brought on from anxeties and unwanted thoughts, as well as tics or Parkinson's disease-like symptoms: rigidity, tremor, jerking arm movements, or involuntary movements of the limbs.

There are many other possible symptoms, and it is not necessary to display those described in the lists below to be considered as suffering from OCD. Formal diagnosis should be performed by a psychologist, a psychiatrist or psychoanalyst. OCD sufferers are aware that their thoughts and behavior are not rational, but they feel bound to comply with them to fend off feelings of panic or dread. Although everyone may experience unpleasant thoughts at one time or another, these are short-lived and fade away in time.For people with OCD, the thoughts are intrusive and persistent, and cause them great anxiety and distress.

Contamination

A major subtype of the fear category is the fear of contamination:(see mysophobia); some sufferers may fear the presence of human body secretions such as saliva, blood, sweat, tears, vomit, or mucus, or excretions such as urine, semen or feces. Some OCD sufferers even fear that the soap they are using is contaminated. These anxiety-driven fears may cause a person to experience significant distress, which may make it difficult for a person with OCD to tolerate a workplace, venture into public locations, or conduct normal social relationships.

Performing tasks

Symptoms related to performing tasks may include repeated hand washing or clearing of the throat; specific counting systems or counting of steps; doing repetitive actions -- more generally, this can involve an obsession with numbers or types of numbers (e.g., odd numbers). These obsessive behaviours can cause individuals to feel psychological distress, because they are very concerned about having "made mistakes" in the number of steps that they have taken, or the number of stairs on a staircase. For some people with OCD, these obsessive counting and re-counting tasks, along with the attendant anxiety and fear, can take hours of each day, which can make it hard for the person to fulfill their work, family, or social roles. In some cases, these behaviours can also cause adverse physical symptoms: people who obsessively wash their hands with antibacterial soap and hot water (to remove germs) can make their skin red and raw with dermatitis.

Intrusive thoughts and fears

Intrusive thoughts are unwelcome, involuntary thoughts, images or unpleasant ideas that may become obsessions, are upsetting or distressing, and can be difficult to be free of and manage. Intrusive thoughts, urges, and images are of inappropriate things at inappropriate times, usually falling into three categories: inappropriate aggressive thoughts, inappropriate sexual thoughts, or blasphemous religious thoughts. Most people experience these thoughts; when they are associated with OCD or depression, they may become paralyzing, anxiety-provoking, and persistent. Many people experience the type of unpleasant or unwanted thoughts that people with more troubling intrusive thoughts have, but most people are able to dismiss these thoughts. When intrusive thoughts co-occur with OCD, patients are less able to ignore the unpleasant thoughts and may pay undue attention to them, causing the thoughts to become more frequent and distressing.

Violent or aggressive thoughts

Intrusive thoughts may involve violent obsessions about hurting others or one's self. They can include such thoughts as harming an innocent child, jumping from a bridge, mountain or the top of a tall building, urges to jump in front of a train or automobile, and urges to push another in front of a train or automobile. A survey of healthy college students found that virtually all of them had intrusive thoughts from time to time, including imagining or wishing harm upon a family member or friend, impulses to attack or kill a small child, or animal, or shout something rude or violent. A person with OCD may meet up with their best friend, to whom they bear no ill will, and an image of them stabbing their friend may "pop" into their head.

While some individuals with OCD who have these unwanted images pop into their minds are able to dismiss the images as random "static" generated by the mind, others are tormented by the thoughts, and they may worry that they are actual desires that they may act on, or that they are "going crazy." In some cases, the person struggling with these horrible images may try to deal with them by developing compulsions. For example, a person who is tormented by unwanted thoughts of them stabbing their mother with a kitchen knife may ensure that all kitchen knives are kept locked away, to prevent the perceived danger that they may "act upon" the horrible thoughts.

The possibility that most patients suffering from intrusive thoughts will ever act on those thoughts is low; patients who are experiencing intense guilt, anxiety, shame, and upset over bad thoughts are different from those who actually act on bad thoughts. The history of violent crime is dominated by those who feel no guilt or remorse; the very fact that someone is tormented by intrusive thoughts, and has never acted on them before, is an excellent predictor that they won't act upon the thoughts. According to Baer, a patient should be concerned that intrusive thoughts are dangerous if the person doesn't feel upset by the thoughts, rather finds them pleasurable; has ever acted on violent or sexual thoughts or urges; hears voices or sees things that others don't see; or feels uncontrollable irresistible anger.

Inappropriate sexual thoughts

Sexual obsessions involve intrusive thoughts or images of "kissing, hugging a lot, touching, fondling, oral sex, anal sex, intercourse, and rape" with "strangers, acquaintances, parents, children, family members, friends, coworkers, animals and religious figures", involving "heterosexual or homosexual content" with persons of any age. Like other intrusive, unpleasant thoughts or images, most people have some inappropriate sexual thoughts at times, but people with OCD may attach significance to the unwanted sexual thoughts, generating anxiety and distress. The doubt that accompanies OCD leads to uncertainty regarding whether one might act on the bad thoughts, resulting in self-criticism or loathing.

One of the more common sexual intrusive thoughts occurs when an obsessive person doubts his or her sexual identity, a symptom of OCD called homosexuality anxiety or HOCD. As in the case of most sexual obsessions, sufferers may feel shame and live in isolation, finding it hard to discuss their fears, doubts, and concerns about their sexual identity. A person experiencing sexual intrusive thoughts may feel shame, "embarrassment, guilt, distress, torment, fear that you may act on the thought or perceived impulse and, doubt about whether you have already acted in such a way." Depression may be a result of the self-loathing that can occur, depending on how much the OCD interferes with daily functioning or causes distress. The possibility that most patients suffering from intrusive thoughts to sexually assault people will ever act on those thoughts is low; patients who are experiencing intense guilt, anxiety, shame, and upset over bad thoughts are different from those who actually act on bad thoughts.

Related conditions

OCD is often confused with the separate condition obsessive-compulsive personality disorder. The two are not the same condition, however. OCD is ego dystonic, meaning that the disorder is incompatible with the sufferer's self-concept. Because disorders that are ego dystonic go against an individual's perception of his/herself, they tend to cause much distress. OCPD, on the other hand, is ego syntonic — marked by the individual's acceptance that the characteristics displayed as a result of this disorder are compatible with his/her self-image. Ego syntonic disorders understandably cause no distress. Persons suffering from OCD are often aware that their behavior is not rational and are unhappy about their obsessions but nevertheless feel compelled by them. Persons with OCPD are not aware of anything abnormal about themselves; they will readily explain why their actions are rational, and it is usually impossible to convince them otherwise. Persons with OCD are ridden with anxiety; persons who suffer from OCPD, by contrast, tend to derive pleasure from their obsessions or compulsions. This is a significant difference between these disorders.

Equally frequently, these rationalizations do not apply to the overall behavior, but to each instance individually; for example, a person compulsively checking their front door may argue that the time taken and stress caused by one more check of the front door is considerably less than the time and stress associated with being robbed, and thus the check is the better option. In practice, after that check, the individual is still not sure, and it is still better in terms of time and stress to do one more check, and this reasoning can continue as long as necessary.

Some OCD sufferers exhibit what is known as overvalued ideas. In such cases, the person with OCD will truly be uncertain whether the fears that cause them to perform their compulsions are irrational or not. After some discussion, it is possible to convince the individual that their fears may be unfounded. It may be more difficult to do ERP therapy on such patients, because they may be, at least initially, unwilling to cooperate. For this reason OCD has often been likened to a disease of pathological doubt, in which the sufferer, while not usually delusional, is often unable to realize fully what sorts of dreaded events are reasonably possible and which are not.

OCD is different from behaviors such as gambling addiction and overeating. People with these disorders typically experience at least some pleasure from their activity; OCD sufferers do not actively want to perform their compulsive tasks, and experience no pleasure from doing so. OCD is placed in the anxiety class of mental illness, but like many chronic stress disorders it can lead to clinical depression over time. The constant stress of the condition can cause sufferers to develop a deadening of spirit, a numbing frustration, or sense of hopelessness. OCD's effects on day-to-day life — particularly its substantial consumption of time — can produce difficulties with work, finances and relationships. There is no known cure for OCD as of yet, but there are a number of successful treatment options available.

Related/Spectrum disorders

People with OCD may be diagnosed with other conditions, such as generalized anxiety disorder, anorexia nervosa, social anxiety disorder, bulimia nervosa, Tourette syndrome, asperger's syndrome, compulsive skin picking, body dysmorphic disorder, trichotillomania, and (as already mentioned) obsessive-compulsive personality disorder. There is some research demonstrating a link between drug addiction and OCD as well. Many who suffer from OCD suffer also from panic attacks. There is a higher risk of drug addiction among those with any anxiety disorder (possibly as a way of coping with the heightened levels of anxiety), but drug addiction among OCD patients may serve as a type of compulsive behavior and not just as a coping mechanism. Depression is also extremely prevalent among sufferers of OCD. One explanation for the high depression rate among OCD populations was posited by Mineka, Watson, and Clark (1998), who explained that people with OCD (or any other anxiety disorder) may feel depressed because of an "out of control" type of feeling.

Some cases are thought to be caused at least in part by childhood streptococcal infections and are termed PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The streptococcal antibodies become involved in an autoimmune process. Though this idea is not set in stone, if it does prove to be true, there is cause to believe that OCD can to some very small extent be "caught" via exposure to strep throat (just as one may catch a cold). However, if OCD is caused by bacteria, this provides hope that antibiotics may eventually be used to treat or prevent it.

Causes

Psychological

Scientists studying obsessive-compulsive disorder are split into two factions disagreeing over the illness's cause. One side believes that obsessive-compulsive behavior is a psychological disorder; the other side thinks it has a neurological origin.

From the 14th to the 16th century in Europe, it was believed that people who experienced blasphemous, sexual, or other obsessive thoughts were possessed by the Devil. Based on this reasoning, treatment involved banishing the "evil" from the "possessed" person through exorcism. In the early 1910s, Sigmund Freud attributed obsessive-compulsive behavior to unconscious conflicts which manifested as symptoms. Freud describes the clinical history of a typical case of "touching phobia" as starting in early childhood, when the person has a strong desire to touch an item. In response, the person develops an "external prohibition" against this type of touching. However, this "prohibition does not succeed in abolishing" the desire to touch; all it can do is repress the desire and "force it into the unconscious".

The cognitive-behavioral model suggests that the behaviour is carried out to remove anxiety-provoking intrusive thoughts. Unfortunately this only brings about temporary relief as the thought re-emerges. Each time the behaviour occurs it is negatively reinforced (see Reinforcement) by the relief from anxiety, thereby explaining why the dysfunctional activity increases and generalises (extends to other, related stimuli) over a period of time. For example, after touching a door-knob a person might have the thought that they may develop a disease as a result of contamination. They then experience anxiety, which is relieved when they wash their hands. This might be followed by the thought "but did I wash them properly?" causing an increase in anxiety once more, the hand-washing once again rewarded by the removal of anxiety (albeit briefly) and the cycle being repeated when thoughts of contamination re-occur. The distressing thoughts might then spread to fear of contamination from e.g. a chair (someone might have touched the chair after touching the door handle).

Biological

There are many different theories about the cause of obsessive-compulsive disorder. The majority of researchers believe that there is some type of abnormality with the neurotransmitter serotonin, among other possible psychological or biological abnormalities; however, it is possible that this activity is the brain's response to OCD, and not its cause. Serotonin is thought to have a role in regulating anxiety, though it is also thought to be involved in such processes as sleep and memory function. In order to send chemical messages, serotonin must bind to the receptor sites located on the neighboring nerve cell. It is hypothesized that OCD sufferers may have blocked or damaged receptor sites that prevent serotonin from functioning to its full potential. This suggestion is supported by the fact that many OCD patients benefit from the use of selective serotonin reuptake inhibitors (SSRIs) — a class of antidepressant medications that allow for more serotonin to be readily available to other nerve cells. For more about this class of drugs, see the section about potential treatments for OCD.

The Stanford University School of Medicine OCD webpage states, "Although the causes of the disorder still elude us, the recent identification of children with OCD caused by an autoimmune response to Group A streptococcal infection promises to bring increased understanding of the disorder's pathogenesis.

Recent research has revealed a possible genetic mutation that could help to cause OCD. Researchers funded by the National Institutes of Health have found a mutation in the human serotonin transporter gene, hSERT, in unrelated families with OCD. Moreover, in his study of identical twins, Rasmussen (1994) produced data that supported the idea that there is a "heritable factor for neurotic anxiety". In addition, he noted that environmental factors also play a role in how these anxiety symptoms are expressed. However, various studies on this topic are still being conducted and the presence of a genetic link is not yet definitely established.

Another possible genetic cause of OCD was discovered in August 2007 by scientists at Duke University Medical Center in North Carolina. They genetically engineered mice that lacked a gene called SAPAP3. This protein is highly expressed in the striatum, an area of the brain linked to planning and the initiation of appropriate actions. The mice spent three times as much time grooming themselves as ordinary mice, to the point that their fur fell off.

Using tools like positron emission tomography (PET scans), it has been shown that those with OCD tend to have brain activity that differs from those who do not have this disorder. This suggests that brain functioning in those with OCD may be impaired in some way. A popular explanation for OCD is that offered in the book Brain Lock by Jeffrey Schwartz, which suggests that OCD is caused by the part of the brain that is responsible for translating complex intentions (e.g., "I will pick up this cup") into fundamental actions (e.g., "move arm forward, rotate hand 15 degrees, etc.") failing to correctly communicate the chemical message that an action has been completed. This is perceived as a feeling of doubt and incompleteness, which then leads the individual to attempt to consciously deconstruct their own prior behavior — a process which induces anxiety in most people, even those without OCD .

It has been theorized that a miscommunication between the orbitofrontal cortex, the caudate nucleus, and the thalamus may be a factor in the explanation of OCD. The orbitofrontal cortex (OFC) is the first part of the brain to notice whether or not something is wrong. When the OFC notices that something is wrong, it sends an initial "worry signal" to the thalamus. When the thalamus receives this signal, it in turn sends signals back to the OFC to interpret the worrying event. The caudate nucleus lies between the OFC and the thalamus and prevents the initial worry signal from being sent back to the thalamus after it has already been received. However, it is suggested that in those with OCD, the caudate nucleus does not function properly, and therefore does not prevent this initial signal from recurring. This causes the thalamus to become hyperactive and creates a virtually never-ending loop of worry signals being sent back and forth between the OFC and the thalamus. The OFC responds by increasing anxiety and engaging in compulsive behaviors in an attempt to relieve this apprehension. This overactivity of the OFC is shown to be attenuated in patients who have successfully responded to SSRI medication. The increased stimulation of the serotonin receptors 5-HT2A and 5-HT2C in the OFC is believed to cause this inhibition.

Some research has discovered an association between a type of size abnormality in different brain structures and the predisposition to develop OCD. Through the use of magnetic resonance imaging (MRI), researchers at Cambridge's Brain Mapping Unit were able to discover distinctive patterns in the brain structure of individuals with OCD and their close family members. This is the first instance in which it has been demonstrated that those with a familial risk of developing OCD have anatomical differences when compared with ordinary individuals. The discovery of these structural differences in the area of the brain associated with stopping motor response may ultimately aid researchers who seek to determine which genes contribute to the development of OCD.

Demographics and other statistics

In a 1980 study of 20,000 adults from New Haven, Baltimore, St. Louis, Durham, and Los Angeles, the lifetime prevalence rate of OCD for both sexes was recorded at 2.5 percent. Education also appears to be a factor. The lifetime prevalence of OCD is lower for those who have graduated high school than for those who have not (1.9 percent versus 3.4 percent). However, in the case of college education, lifetime prevalence is higher for those who graduate with a degree (3.1 percent) than it is for those who have only some college background (2.4 percent). As far as age is concerned, the onset of OCD usually ranges from the late teenage years until the mid-20s in both sexes, but the age of onset tends to be slightly younger in males than in females.

Violence is very rare among OCD sufferers, but the disorder is often debilitating to their quality of life. Also, the psychological self-awareness of the irrationality of the disorder can be painful. For people with severe OCD, it may take several hours a day to carry out the compulsive acts. To avoid perceived obsession triggers, they also often avoid certain situations or places altogether. It has been alleged that sufferers are generally of above-average intelligence, as the very nature of the disorder necessitates complicated thinking patterns

Treatment

According to the Expert Consensus Guidelines for the Treatment of obsessive-compulsive disorder, behavioral therapy (BT), cognitive therapy (CT), medications are first-line treatments for OCD. Psychodynamic psychotherapy may help in managing some aspects of the disorder, but there are no controlled studies that demonstrate effectiveness of psychoanalysis or dynamic psychotherapy in OCD.

Behavioral therapy

The specific technique used in BT/CBT is called exposure and ritual prevention (also known as "exposure and response prevention") or ERP; this involves gradually learning to tolerate the anxiety associated with not performing the ritual behavior. At first, for example, someone might touch something only very mildly "contaminated" (such as a tissue that has been touched by another tissue that has been touched by the end of a toothpick that has touched a book that came from a "contaminated" location, such as a school.) That is the "exposure". The "ritual prevention" is not washing. Another example might be leaving the house and checking the lock only once (exposure) without going back and checking again (ritual prevention). The person fairly quickly habituates to the anxiety-producing situation and discovers that their anxiety level has dropped considerably; they can then progress to touching something more "contaminated" or not checking the lock at all — again, without performing the ritual behavior of washing or checking.

Exposure and ritual/response prevention has been demonstrated to be the most effective treatment for OCD. It has generally been accepted that psychotherapy, in combination with psychotropic medication, is more effective than either option alone. However, more recent studies have shown no difference in outcomes for those treated with the combination of medicine and CBT versus CBT alone.

Medication

Medications as treatment include selective serotonin reuptake inhibitors (SSRIs) such as paroxetine (Seroxat, Paxil, Xetanor, ParoMerck, Rexetin), sertraline (Zoloft, Stimuloton), fluoxetine (Prozac, Bioxetin), escitalopram (Lexapro), and fluvoxamine (Luvox) as well as the tricyclic antidepressants, in particular clomipramine (Anafranil). SSRIs prevent excess serotonin from being pumped back into the original neuron that released it. Instead, serotonin can then bind to the receptor sites of nearby neurons and send chemical messages or signals that can help regulate the excessive anxiety and obsessive thoughts. In some treatment-resistant cases, a combination of clomipramine and an SSRI has shown to be effective even when neither drug on its own has been efficacious. There has been controversy of efficacy with this class of drugs, recent studies of SSRIs have suggested a low profile for efficacy and high profile for dangerous side effects.

Benzodiazepines are also used in treatment. It's not uncommon to administer this class of drugs during the "latency period" for SSRIs or as synergistic adjunct long-term. Although widely prescribed, benzodiazepines have not been demonstrated as an effective treatment for OCD and can be addictive.

Serotonergic antidepressants typically take longer to show benefit in OCD than with most other disorders which they are used to treat, as it is common for 2–3 months to elapse before any tangible improvement is noticed. In addition to this, the treatment usually requires high doses. Fluoxetine, for example, is usually prescribed in doses of 20 mg per day for clinical depression, whereas with OCD the dose will often range from 20 mg to 80 mg or higher, if necessary. In most cases antidepressant therapy alone will only provide a partial reduction in symptoms, even in cases that are not deemed treatment-resistant. Other medications such as riluzole, memantine, gabapentin (Neurontin), lamotrigine (Lamictal), and low doses of the newer atypical antipsychotics olanzapine (Zyprexa), quetiapine (Seroquel) and risperidone (Risperdal) have also been found to be useful as adjuncts in the treatment of OCD.

The use of antipsychotics in OCD must be undertaken carefully, however, since, although there is very strong evidence that at low doses they are beneficial (most likely due to their dopamine receptor antagonism), at high doses these same antipsychotics have proven to cause dramatic obsessive-compulsive symptoms even in those patients who do not normally have OCD. This is most likely due to the antagonism of 5-HT2A receptors becoming very prominent at these doses and outweighing the benefits of dopamine antagonism. Another point that must be noted with antipsychotic treatment is that SSRIs inhibit the chief enzyme that is responsible for metabolising antipsychotics — CYP2D6 — so the dose will be effectively higher than expected when these are combined with SSRIs. Also, it must be noted that antipsychotic treatment should be considered as augmentation treatment when SSRI treatment does not bring positive results.

Alternative Drug Treatments

The naturally occurring sugar inositol may be an effective treatment for OCD. Inositol appears to modulate the actions of serotonin and has been found to reverse desensitisation of the neurotransmitter's receptors. St John's Wort has been claimed to be of benefit due to its (non-selective) serotonin re-uptake inhibiting qualities, and studies have emerged that have shown positive results. However, a double-blind study, using a flexible-dose schedule (600-1800 mg/day), found no difference between St John's Wort and the placebo. Studies have also been done that show nutrition deficiencies may also contribute to OCD and other mental disorders. Certain vitamin and mineral supplements may aid in such disorders and provide the nutrients necessary for proper mental functioning.

Recent research has found increasing evidence that opioids may significantly reduce OCD symptoms, though the use of them is not sanctioned for treatment and considered an "off-label" use, factors being physical dependence and long term drug tolerance. Anecdotal reports suggest that some OCD sufferers have successfully self-medicated with opioids such as tramadol (Ultram) and hydrocodone (Vicodin, Lortab), though the off-label use of such painkillers is not widely accepted, research on this has been limited. Tramadol is an atypical opioid that may be a viable option as it has a low potential for abuse and addiction, mild side effects, and shows signs of rapid efficacy in OCD. Tramadol not only provides the anti-OCD effects of an opiate, but also inhibits the re-uptake of serotonin (in addition to norepinephrine). This may provide additional benefits, but should not be taken in combination with antidepressant medication unless under careful medical supervision due to potential serotonin syndrome.

Recent studies at the University of Arizona using the tryptamine alkaloid psilocybin have shown promising results. There are reports that other hallucinogens such as LSD and peyote have produced similar benefits. It has been hypothesised that this effect may be due to stimulation of 5-HT2A receptors and, less importantly, 5-HT2C receptors. This causes, among many other effects, an inhibitory effect on the orbitofrontal cortex, an area of the brain in which hyperactivity has been strongly associated with OCD.

Emerging evidence suggests that regular nicotine treatment may be helpful in improving symptoms of OCD, although the pharmacodynamical mechanism by which this improvement is achieved is not yet known, and more detailed studies are needed to fully confirm this hypothesis. Anecdotal reports suggest OCD can worsen when cigarettes are smoked as a way of obtaining nicotine.

Psychosurgery

For some, neither medication, support groups nor psychological treatments are helpful in alleviating obsessive-compulsive symptoms. These patients may choose to undergo psychosurgery as a last resort. In this procedure, a surgical lesion is made in an area of the brain (the cingulate bundle). In one study, 30% of participants benefited significantly from this procedure. Deep-brain stimulation and vagus nerve stimulation are possible surgical options which do not require the destruction of brain tissue, although their efficacy has not been conclusively demonstrated.

In the US, psychosurgery for OCD is a treatment of last resort and will not be performed until the patient has failed several attempts at medication (at the full dosage) with augmentation, and many months of intensive cognitive-behavioral therapy with exposure and ritual/response prevention. Likewise, in the UK, psychosurgery cannot be performed unless a course of treatment from a suitably qualified cognitive-behavioural therapist has been carried out.

Transcranial magnetic stimulation

Though in its early stages of research, Transcranial magnetic stimulation (TMS) has shown promising results. The magnetic pulses are focused on the brain's supplementary motor area (SMA), which plays a role in filtering out extraneous internal stimuli, such as ruminations, obsessions, and tics. The TMS treatment is an attempt to normalize the SMA's activity, so that it properly filters out thoughts and behaviors associated with OCD.

Neuropsychiatry

OCD primarily involves the brain regions of the striatum, the orbitofrontal cortex and the cingulate cortex. OCD involves several different receptors, mostly H₂, M₄, NK₁, NMDA, and non-NMDA glutamate receptors. The receptors 5-HT_1D, 5-HT_2C, and the μ opioid receptor exert a secondary effect. The H₂, M₄, NK₁, and non-NMDA glutamate receptors are active in the striatum, whereas the NMDA receptors are active in the cingulate cortex.

The activity of certain receptors is positively correlated to the severity of OCD, whereas the activity of certain other receptors is negatively correlated to the severity of OCD. Correlations where activity is positively correlated to severity include the histamine receptor (H₂); the Muscarinic acetylcholine receptor(M₄); the Tachykinin receptor (NK₁); and non-NMDA glutamate receptors. Correlations where activity is negatively correlated to severity include the NMDA receptor (NMDA); the Mu opioid receptor (μ opioid); and two types of 5-HT receptors (5-HT_1D and 5-HT_2C) The central dysfunction of OCD may involve the receptors nk1, non-NMDA glutamate receptors, and NMDA, whereas the other receptors could simply exert secondary modulatory effects.

Pharmaceuticals that act directly on those core mechanisms are aprepitant (nk1 antagonist), riluzole (glutamate release inhibitor), and tautomycin (NMDA receptor sensitizer). Also, the anti-Alzheimer's drug memantine is being studied by the OC Foundation in its efficacy in reducing OCD symptoms due to it being an NMDA antagonist. One case study published in The American Journal of Psychiatry suggests that "memantine may be an option for treatment-resistant OCD, but controlled studies are needed to substantiate this observation. The drugs that are popularly used to fight OCD lack full efficacy because they do not act upon what are believed to be the core mechanisms.

Notable cases

David Beckham has been outspoken regarding his struggle with OCD, and has told media that he has to count all his clothes, and magazines have to lie in a straight line. He can not have more soda cans in the fridge than three, and if there are any more at home they have to be placed in a cupboard. He has explained that the reason he keeps getting more tattoos, is that he feels addicted to the pain of the needle. In hotels, any books that are on a shelf must be placed in the drawer. He has expressed that he wants to get help for his problems.

Howard Hughes is known to have suffered from OCD and it is believed that his mother may have also been a sufferer. Friends of Hughes have mentioned his obsession with minor flaws in clothing and he is reported to have had a great fear of germs, common among OCD patients..