Since the incidence of more serious side effects also varies among these agents, both the side effect risks and effectiveness of these drugs should be taken into account when considering drug options. A potentially serious but uncommon side effect is a heart rhythm abnormality, referred to as the long QTc syndrome . The overall incidence of extrapyramidal symptoms is infrequent compared to the preceding generation of antipsychotic compounds, but still remain a problem.
Table 2 provides comparisons of side effect frequencies among AAPs. Table 2. It is highly specific for certain dopamine receptors and blocks dopamine signal transmission. Two published clinical studies, one from and the other , show very encouraging results although neither study was controlled. Both investigations used amisulpride as augmentation treatment in SSRI resistant patients. After 12 weeks of treatment, patients with baseline moderate to severe OCD average score The most commonly observed side effects included weight gain, mild sedation and asthenia  , and like the other AAPs, there is an increased risk of developing extrapyramidal side effects.
Sexual side effects were infrequently observed. These results are promising and, if the effects of this combined treatment were confirmed in better-designed studies, it would rank among the most effective adjunctive OCD therapies. There is rapidly growing interest in the use of drugs that specifically target NT in several distinct ways.
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Several show promise for OCD treatment and, in general, their side effect properties are quite modest. D-cycloserine appears to alter NT function in a manner that accelerates extinction learning. Extinction learning, or conditioning, occurs when a stimulus for a particular action such as an obsession is not followed by the conditioned response the compulsion. Extinction learning is a fundamental part of ERP therapy.
Although clinical research studies of D-cycloserine have thus far been mixed, some show that the combination of ERP and D-cycloserine results in at least a doubling of the rate of improvement compared to ERP alone and may be considerably faster in the early part of ERP treatment 59, Thus, there is little to no evidence that D-cycloserine significantly enhances the effectiveness of ERP. Rather, it appears to enhance extinction learning thereby enabling the patient to more quickly improve and, perhaps, even shorten the required duration of the ERP treatment course. Current guidelines from the American Psychological Association include the recommendation that to be an effective adjunct for ERP, D-cycloserine should be administered not more than 2 hours before ERP; little to no treatment effect is seen if it is given 4 or more hours before ERP.
Several studies of the addition of memantine to SSRI have shown generally favourable responses in one-third to two-thirds of treated. A more recent double blind, placebo-controlled study examined the effect of adding memantine to a SSRI fluvoxamine for patients with moderate to severe OCD It is unfortunately difficult to completely compare these findings to other drug studies because the trial period was only eight weeks rather than the more usual 12 necessary for SSRI studies. In addition, not all of the studied patients were SSRI resistant. Nonetheless, preliminary findings suggest that adjunctive memantine shows considerable promise in treatment resistant patients.
Obsessive compulsive disorder (OCD) - NHS
The frequency and type of reported mild side effects did not differ between patient groups, suggesting that memantine might be better tolerated in patients intolerant to other agents. Riluzole is another drug that affects glutamate by preventing its release from storage sites. At present, its effectiveness as therapy for OCD has had mixed results 66 , although significant symptom responses have been reported for both depression and OCD in children and adults As with most of the other drugs used to treat OCD it is, as yet, unknown why some patients respond to specific drugs and others do not.
This also is why drug trial and error for treatment-resistant patients is highly advisable for those whose symptoms continue to be distressing. Among other drugs of several classes that have been used to treat OCD, several have attracted interest. This drug is an anti-seizure medication and is also used for bipolar disorder and the prevention of migraine headaches. The use of topiramate as add-on treatment for OCD is based on several of its actions that result in diminished glutamate activity and increased GABA actions.
There are conflicting results from several recent controlled studies.
In one, there was little clinically or statistically significant improvement with the addition of topiramate to an SSRI In another report, there was significant improvement on the Y-BOCS compulsions subscale but not the obsessions subscale Troublesome side effects include influenza-like symptoms, paresthesias  , difficulties with memory, and distorted taste sensation. It is also worth noting that the average treatment time until full drug effect may take several months. Lamotrigine is an anti-seizure drug and mood stabiliser.
Its actions result in decreased glutamate levels and interference with glutamate neurotransmission. It has been used successfully in bipolar disorder.
Reports of lamotrigine as an effective add-on treatment for OCD show mixed results. Several controlled studies have been completed. In one such study, SSRI-treated patients with moderately severe to severe OCD received lamotrigine or placebo as add-on therapy over 14 weeks. Another study showed similar results 72 but non-response has also been reported These were generally mild and transient, and included sedation, fatigue, headache, and skin rash.
The optimal OCD lamotrigine doses remain unclear, although higher doses may result in better responses Given the levels of overall improvement generally observed, and its modest side effect profile, lamotrigine appears to merit consideration when other drugs are ineffective. This drug is mainly used to control nausea and vomiting, especially when associated with cancer chemotherapy, radiotherapy and other conditions.
The interest in ondansetron as a possible OCD drug is due to its actions that result in reduced nerve transmission by dopamine. As an augmentation agent, several uncontrolled studies showed, at best, only modest improvement from the addition of ondansetron to an SSRI By contrast, two controlled, randomized studies of severe OCD compared the combination of ondansetron and fluvoxamine to fluvoxamine alone 76, The findings from both studies showed substantial and highly significant improvements of Y-BOCS scores for the combination compared to the fluvoxamine group.mamelsodi.tk
Aripiprazole Augmentation Effective in Treatment of Comorbid Bipolar Disorder, OCD
Of particular interest, when patients were retested following discontinuation of ondansetron treatment, most of the improvement achieved on treatment was lost. Common side effects seen with treatment include headache, constipation, and abdominal pain. The high doses of ondansetron that have shown efficacy in clinical trials also increase the possibility of long QTc heart arrhythmias in at-risk patients.
Although granisetron has actions similar to ondansetron, it differs in its ability to cross readily from the blood into the spinal fluid that bathes the brain. There appears to be only one study of granisetron in moderate to severe OCD in which one group of patients received granisetron and fluvoxamine and another fluvoxamine alone for eight week More modestly improved scores were also seen in the fluvoxamine-only group.
This drug stimulates GABA production, thereby inhibiting glutamate release.
Several case reports and case series have demonstrated improvement of OCD symptoms when combined with an SSRI with or without an atypical antipsychotic, suggesting a possible role for this drug in patients with resistance to multiple drugs. To date, however, recommendations would be very premature and based on insufficient data.
A placebo-controlled study of pregabalin in SSRI resistant patients appears to be underway, the results of which will hopefully better define its effect on outcomes.
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A member of the beta-blocker class of medications, pindolol is primarily used to treat high blood pressure. It also promotes the release of serotonin in the brain, which is the basis for its inclusion in this report. Several small case studies have shown a statistically significant but rather modest improvement of Y-BOCS scores. In two placebo controlled studies there was a non-statistical trend of improvement after the addition of pindolol to an SSRI. Lithium interacts with neurotransmitters in several complex ways, and results in reduced availability of dopamine and glutamate, the stimulatory NTs, while increasing GABA levels.
Based on this mechanism of action, lithium has been evaluated for OCD treatment. Much of this interest comes from reports of improved OCD-like symptoms in bipolar disorder. However, at least two clinical trials failed to show any clinically significant improvement using add-on lithium for patients with primary OCD. Thus, there is no convincing evidence to support its usefulness as OCD add-on treatment, and further raises the question of whether the OCD symptoms associated with bipolar-disorder, and those in primary OCD, occur as the result of different or unrelated mechanisms.
One additional comment: since symptoms of OCD may overlap, or occur concurrently, with bipolar disorder and several other mental health disorders, treatment with lithium may be worth consideration in such mixed disorders. Psychological treatment techniques alone, or in combination with drug and other therapies, have long been an integral part of treatment for OCD, particularly of a moderate to severe degree. These methods have traditionally been categorised as either cognitive CT or behavioural BT therapies .
Numerous studies have compared the effectiveness of various CT and BT techniques, in general finding that both result in favourable responses, although BT and in particular ERP has shown superior results 24, Arnold, P. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Archives of General Psychiatry, 63 7 , Fontenelle, L. Role of stressful and traumatic life events in obsessive—compulsive disorder. Neuropsychiatry, 1 1 , Grados, M.
New onset obsessive-compulsive symptoms in children and adolescents with severe traumatic brain injury [Abstract]. Hollander, E. Kellner, M.
Stuck in a Loop of ‘Wrongness’: Brain Study Shows Roots of OCD
Drug treatment of obsessive-compulsive disorder. Dialogues in Clinical Neuroscience, 12 2 , Markarian, Y. Multiple pathways to functional impairment in obsessive-compulsive disorder. Clinical Psychology Review, 30 1 , Moretti, G. Murphy, D. Obsessive-compulsive disorder and its related disorders: a reappraisal of obsessive-compulsive spectrum concepts.
Dialogues Clinical Neuroscience, 12 2 , Nestadt, G. A family study of obsessive-compulsive disorder. Archive of General Psychiatry , 57 4 , OCD at school - a primer for educators. Parmet, S. The different types of obsessive-compulsive disorder. Treatments for OCD: Medications. What causes OCD? What you need to know about obsessive compulsive disorder. MLA Nichols, Hannah. MediLexicon, Intl. APA Nichols, H.