Buspirone SSRIs

Non-FDA approved but commonly used trazodone, buspirone, SSRIs. 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

To overcome these side effects, buspirone has to be gradually titrated for several days or weeks until it reaches the therapeutic dose, taking weeks for the drug to be effective and not always reaching a fully effective dose. Its short half-life in humans necessitates three-times a day (tid) dosage, which also makes it less attractive compared to the once a day dosage of SSRIs. 

Buspirone does not share any of the problematic benzodiazepine properties such as sedation, motor impairment, addiction, physical dependence, or withdrawal. The most common side effects of buspirone include dizziness, nausea, headache, fatigue, and dry mouth. Despite its activity in the serotonin system, buspirone is not associated with the sexual side effects that plague the SSRIs, SNRIs, MAOIs, and TCAs. 

Buspirone. Although initial open label results were promising, a controlled study of buspirone, approved by the FDA for treatment of GAD, failed to demonstrate any effectiveness in the treatment of social anxiety disorder. However, a subsequent controlled study indicated that buspirone administered at 30-60 mg/day is an effective augmentation strategy for patients with social anxiety disorder who have only experienced a partial response to SSRI therapy. 

Agitation (acute, mild) Trazodone Lorazepam Buspirone Sodium divalproex SSRI ... 

With regard to generalized anxiety disorder, it has been postulated that an overactivity of the stimulatory 5-HT pathways occurs. Drugs such as buspirone and ipsapirone are effective in such conditions because they stimulate the inhibitory S-HT a autoreceptors on the raphe nuclei and thereby reduce serotonergic function. It is noteworthy that the SSRIs often worsen anxiety initially because they temporarily enhance serotonergic function. Adaptive changes in the pre- and postsynaptic 5-HT receptors then occur leading to a reduction in the anxiety state. 

Add buspirone to a standard antidepressant (usually an SSRI). The evidence in favour of this combination is largely anecdotal. 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

Bruxism mainly occurs in stage 2 sleep and REM sleep (Bader et ah, 1977). A relationship to stress and anxiety has been suggested, but the disorder can be chronic without apparent association with stress (Faulkner, 1990 Pierce et ah, 1995). It has been suggested that the central dopaminergic system may be involved in the modulation of sleep bruxism (Lobbezoo et al., 1997). Case reports indicate that bruxism can be induced by the SSRI paroxetine (Romanelli et al., 1996). The mechanism remains unclear possibilities include sleep disturbance, serotonergic-mediated inhibition of dopamine manifesting as akathisia, and SSRI-induced anxiety. SSRI-induced bruxism may respond to therapy with buspirone (Ellison et al., 1993). 

Treatment of anxiety disorders in children with psy-chopharmacologic agents has become much more common in the past decade. There are few studies of the use of these drugs in typically developing children and even fewer in children with MR. Most recommendations are based on experience with adults with a dual diagnosis or with typically developing children. The classes of medications used for the treatment of anxiety disorders include SSRIs, benzodiazepines, TCAs, and buspirone. In the Expert Consensus Guidelines (Rush and Frances, 2000), the SSRIs were rated as a first-line treatment for anxiety disorders. Buspirone was also a first-line treatment, with the benzodiazepines considered second line. 

Generalized anxiety disorder Buspirone, benzodiazepines, venlafaxine, SSRIs... 

Social phobia SSRIs, MAOIs, benzodiazepines, buspirone, venlafaxine... 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

Landen M, Bjorling G, Agren H, et al. A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. J Clin Psychiatry 1998 59 664-668. 

In addition to buspirone and the non-barbituate, non-BZP hypnotics, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and other new antidepressants all represent attempts to achieve anxiolytic and hypnotic effects seen with the BZDs, while avoiding their unwanted properties. 

If serotonin is very low or depleted from serotonergic neurons in depression, there would not be much of it released for an SSRI to block its reuptake (Fig. 7—31). Thus, there would theoretically be inadequate desensitization of somatodendritic 5HT1A autoreceptors. Unlike the SSRIs, which are all dependent for their actions on the endogenous release of serotonin, buspirone is not dependent on serotonin levels because it has direct actions on 5HT1A receptors (Fig. 7—32). Thus, buspirone may be able to kick start the desensitization process directly. Initially,... 

Thus, buspirone is synergistic with the SSRIs (Fig. 7—33). To the extent that buspirone is a partial agonist and thus partially blocks the 5HT1A autoreceptors, it... 

FIGURE 7—31- Mechanism of action of buspirone augmentation—part 1. SSRIs act indirectly by increasing synaptic levels of 5HT that has been released there. If 5HT is depleted, there is no 5HT release, and SSRIs are ineffective. This has been postulated to be the explanation for the lack of SSRI therapeutic actions or loss of therapeutic action of SSRI ( poop out ) in some patients. 

FIGURE 7—33. Mechanism of action of buspirone augmentation—pact 3. Shown here is how buspirone potentiates ineffective SSRI action at 5HT1A somatodendritic autoreceptors, resulting in the desired disinhibition of the 5HT neuron. This combination of 5HT1A agonists plus SSRIs may be more effective, not only in depression but also in other disorders treated by SSRIs, such as obsessive-compulsive disorder and panic. 

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